SNÍŽENÍ OBEZITY - protektivní
Metabolic Balance®
Komplexní systém stravování pro úpravu metabolismu a vhodnou redukci hmotnosti bez běžných vedlejších účinků mnohých diet, jako je hladovění, ztráta svaloviny a jo-jo efekt.Metoda Metabolic Balance® byla vyvinuta v Německu Dr. Funfackem. Od roku 2001 se z Německa s velkým úspěchem rozšířila téměř po celém světě jako jedna z nejefektivnějších metod rozumné redukce a udržení hmotnosti, normalizace metabolizmu a prevence tzv. civilizačních onemocnění.
Na základě syntézy ajurvédské typologie, moderních výživových lékařských doporučení a odběru Vaší krve je pomocí softwarové databáze sestaven individuální jídelní plán s dostatkem bílkovin, vitamínů, vlákniny z potravin s nízkou glykemickou náloží. Jídelní plán Metabolic Balance® není postaven na zákazech, ale na sestavení individuálního seznamu vhodných potravin ke konzumaci.
Díky výběru potravin s nízkou glykemickou zátěží má Metabolic Balance® regenerační vliv na náš organismus, obzvláště na chronická onemocnění. Vhodné složení stravy v jídelním plánu Metabolic Balance® tak umožňuje jíst jenom 3x denně a zajišťuje plynulý úbytek hmotnosti, aniž bychom hladověli.
Software při sestavování seznamu vhodných potravin zohledňuje i některé z hodnot krevních testů, míry a zdravotní stav klienta. Pomáhá tak cíleným výběrem potravin normalizovat metabolické odchylky. Dalším kouzlem jídelních plánů Metabolic Balance® je, že není nutné zdlouhavé počítání kilojoulů. V plánech je již spočítáno, kolik gramů kterého typu potraviny jíst.
Metabolic Balance® program je členěn do 4 fází. 4. fáze trvá do konce života. Vyhotovení jídelního plánu Metabolic Balance® stačí jedenkrát za život. Plán se sestavuje v době, kdy klient netrpí žádným onemocněním a po dobu programu je pravidelně sledován lékařem s možností denní konzultace.
Více informací
ADIPOQ polymorfismus
- Příznivá varianta genu ADIPOQ
- Jeidnci mohou tělesnou hmotnost účinně snížit dostatečným příjmem olejů bohatých na mononenasycené MK
- Cca snížit BMI o přibližně 1,5 kg/m2
- Mírně vyšší příjem mononenasycených tuků je pak příznivým vlivem při snižování hmotnosti
- Kyselina olejová (např. v olivovém oleji)
DM je heterozygot
Abarema cochliacarpos (Gomes) Barneby & J.W. Grimes
- Fabaceae
- Barbatimao
- Brazil [99]
Acacia mearnsii De Wild.
- Acácia negra
- South Africa, Australia, Bolivia, Brazil, China, Ecuador, Espanha, United States, Ethiopia, India, Jamaica, Pakistan, Portugal, Quenia, Ruanda, Sri Lanka, Suíça, Taiwan, Tanzânia, Uganda, Zambia [99]
Akebia quinata (Houtt.) Decne.
- Videira de chocolate
- China, South Korea, United States, Japan [99]
- Lardizabalaceae
Alpha-melanocyte-stimulating hormone (alphaMSH)
- Produced by ARC neurons
- To neurons expressing melanocortin 4 receptor (MC4-R)
- Melanocortin 3 receptor (MC3-R)
- Required for leptin anorexigenic function
Amorphophallus konjac K. Koch.
- Konjac
- China [99]
- Araceae
Baccharis articulata (Lam.) Pers.
- Carquejinha, carqueja-doce, carqueja branca
- Argentina
Baccharis trimera (Less.) DC.
- Carqueja, carqueja, amargosa
- Argentina, Bolivia, Brazil, Paraguay, Uruguay [99]
Bidens bipinnata L.
- Carrapicho-de-agulha, picao
- Brazil, Cambodia, China, North Korea, Ecuador, United States, Laos, Madagascar, Nepal, Thailand, Venezuela [99]
Campomanesia xanthocarpa Mart. ex O.Berg.
- Myrtaceae
- Guabiroba
- Argentina, Bolivia, Brazil, Paraguay, Uruguay [99]
Casearia sylvestris Sw.
- Salicaceae
- Guaçatonga, chililo
- Argentina, Belize, Bolivia, Brazil, Colôbia, Costa Rica, Cuba, Ecuador, United States, El Salvador, Guatemala, Suriname, Guiana, French Guiana, Haiti, Honduras, Ilha Caiman, Virgin Islands, India, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Suriname, Trinidad and Tobago, Venezuela, Uruguay [99]
Cassia nomame (Makino) Kitag.
- Cassia
- China [99]
Celastraceae
- Tripterygium wilfordi Hook. f. Lei gong teng Burma,
- China, South Korea, Japan [99]
Cinnamomum cassia (L.) D. Don.
- Lauraceae
- Cassia chinesa
- China, India, Indonesia, Laos, Malaysia, Taiwan, Thailand, Vietnam [99]
Citrus aurantium L.
- Rutaceae
- Laranja de sevilha, laranja-amarga, laranja azeda
- Argentina, Belize, Bolivia, Brazil, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, United States, Guatemala, Honduras, India, Madagascar, Mexico, Panama, Paraguay, Peru, Venezuela [99]
Citrus decumana Murr.
- Pomelo
- China [99]
Cocaine amphetamine related transcript (CART)
- Anorexigenic polypeptide
- Regulated by leptin (Kristensen et al., 1998)
- CART regulates body weight in mice (Asnicar et al., 2001)
- Expression in the hypothalamus is regulated by leptin (Kristensen et al., 1998)
Cart-deficient mice
- Develop, on a high fat diet, a mild obesity (Asnicar et al., 2001)
Coix lacryma-jobi L.
- Conta de lágrima, lágrima de nossa senhora, tsiku
- South Africa, Argentina, Australia, Barbados, Belize, Bolivia, Brazil, Buthan, Burma, Chile, China, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, United States, Ethiopia, Philippines, Gabon, Guatemala, Guiana, French Guiana, Honduras, India, Jamaica, Japan, Laos, Madagascar, Mexico, Nepal, Nicaragua, Papua New Guinea, Paraguay, Peru, Puerto Rico, Sri Lanka, Suriname, Thailand, Turkey, Uruguay, Venezuela, Vietnam [99]
- Poaceae
Costus spicatus (Jacq.) Sw.
- Cana-de-macaco
- Bolivia, Honduras, Mexico, Dominican Republic [99]
- Costaceae
Croton gnaphalii Baill.
- Infalivina Brazil [99]
- Euphorbiaceae
Cuphea carthagenensis (Jacq.) J.F. Macbr.
- Sete sangrias
- Argentina, Bolivia, Brazil, Colombia, Costa Rica, Ecuador, United States, El Salvador, Guatemala, Guiana, French Guiana, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Taiwan, Trinidad and Tobago, Venezuela [99]
Curtisia dentata (Burm.f.) C.A. Sm.
- Assega
-South Africa [99]
-Curtisiaceae
Cymbopogon citratus (DC.) Stapf.
-Capim-limao
-Argentina, Australia, Barbados, Belize, Bolivia, Brazil, Chile, China, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, United States, Philippines, Gabon, Guatemala, Guiana, French Guiana, Honduras, India, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Suriname, Uruguay, Venezuela [99]
Cynara scolymus L.
- Alcachofra
- Colombia, Ecuador, United States [99]
Dioscorea nipponica Makino
- Chuan long shu yu
- Chile, North Korea, Japan, Russia [99]
- Dioscoreaceae
Dioscorea speciosa (L.) Pers.
- Lythraceae
- Rasedá gigante
- Australia, Belize, China, Colombia, Costa Rica, El Salvador, United States, Philippines, Guatemala, Guiana, Honduras, India, Malaysia, Mexico, Nicaragua, Panama, Sri Lanka, Vietnam [99]
Echinodorus macrophyllus (Kunth) Micheli.
- Alismataceae
- Chapéu-de-couro
- Argentina, Bolivia, Brazil, Colombia, Guiana, Honduras, Nicaragua, Paraguay, Peru, Suriname, Venezuela [99]
Equisetum giganteum L.
- Cola de cavalo, rabo de cavalo
- Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Haiti, Honduras, Jamaica, Nicaragua, Panama, Paraguay, Peru [99]
- Equisetaceae
Erythroxylum argentinum O.E. Schulz.
- Cocao, fruta de pomba, baga de pomba
- Argentina, Bolivia, Brazil [11]
- Erythroxylaceae
Foeniculum vulgare Mill.
- Apiaceae
- Funcho, erva doce, anís
- South Africa, Belize, Bolivia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Ecuador, El Salvador, United States, Guatemala, Honduras, Mexico, Peru [99]
Fortunella japonica (Thunb.) Swingle.
- Kumkat
- Honduras [99]
Forxiga (Dfagliflozin)
- Glykosurikum
- Výborný efekt jako pomocník s držením diety pokud po nějaké potravině vyskočí glykémie víc než je žádoucí
- Snižuje chuť k jídlu, otoky, hyperglykemii a mírně i k. močovou
- Takže jsem po tom cekově méně unavená a snáze se mi dodržuje dieta
- Pomáhá mi s návratem do stavu fit - smaozřejmě bez diagnozy diabetu, tedy off-label
- Zatím nejlepší doplněk nebo medikament, co jsem zkusila a citelně pomohl
Fucus vesiculosus L. Bodelha,
- Fava do mar [99]
- Fucaceae
Garcinia cambogia Desr.
- Malabar tamarindo ou goraka [99]
- Clusiaceae
Geraniaceae
- Geranium nepalense Sweet. Ni bo er lao guan cao
- Afeghanistan, Brazil, Burma, China, United States, India, Mongolia, Laos, Pakistan, Sri Lanka, Thailand, Vietnam [99]
Gymnema sylvestre R. Br.
- Apocynaceae
- Gimena
- South Africa, Madagascar [99]
Hibiscus sabdariffa L.
- Caruru-azedo, quiabo-azedo, quiabo-roxo, rosélia e vinagreira [99]
- Malvaceae
Hieracium pilosella L.
- Erva criminosa, orelha de rato
- Canada, Chile, United States [99]
Hoodia gordonii (Masson) Sweet ex Decne.
- Cacto do sul
- South Africa [99]
Ilex paraguariensis A. St.-Hil.
- Aquifoliaceae
- Erva mate, mate
- Argentina, Bolivia, Brazil, Colombia, Ecuador, Peru, Paraguay, Uruguay [99]
Irisin
- Cleavage product of the transmembrane protein fibronectin type-III domain containing protein 5 (FNDC5)
- Physical exercise was able to increase the skeletal muscle expression of: [6]
- Several genes involved in energy expenditure
- FNDC5, located on locus 1p35.1 [6]
- Expressed as a consequence of PGC-1? activation
- Cleaved and released in the circulation in the form of irisin
- Acting on subcutaneous adipose tissue [6]
- Induce browning
- Increased thermogenesis and energy expenditure [6]
- FNDC5 overexpression
- Through viral vectors
- Decreased fat mass
- Improved glucose tolerance in diet-induced obese and insulin resistant mice [6]
- Irisin strongly increased a browning response in brite but not in brown adipocytes
- Stimulation of irisin secretion by
- Cold
- Exercise [6]
- Irisin secretion
- Results from PGC-1a activation [6]
- FNDC5 in mice is preferably expressed by oxidative muscles
- Fenofibrate
- PPAR-? agonist = activator of PGC-1 alfa [6]
- Increase
- Serum irisin [6]
- UCP-1 expression in mice [6]
- Serum concentrations in various studies from 0.04 ng/mL to 2.158 ng/mL
- Possibly due to the different enzyme immunoassay kits used [6]
- Several studies performed in human subjects have not confirmed the role of irisin in promoting browning
- Circulating irisin levels
- Decreased after the training program
- Superior increase after acute exercise
- Endurance exercise is more efficient than short term high intensity exercise in inducing irisin secretion
- Cold-induced raise serum irisin levels
- Highest in subjects reporting shivering [6]
- Muscle contraction-dependent mechanism [6]
- Exercise intensity is positively correlated with the serum irisin raise, independently of energy consumption
- All of these studies used an aerobic exercise program
- Soliciting preferably oxidative muscle fibers [6]
- Chronic exercise training
- Does not seem to be correlated with higher serum irisin levels
- Adaptive mechanism:
- Less dependent of irisin for lipid metabolism
- Or more sensitive to irisin action. [6]
- Irisin also seems to act on the skeletal muscle itself
- Induces AMPK phosphorylation
- Glucose uptake in cultured human skeletal muscle cells
- Induce fatty acid uptake
- Increase of oxidative metabolism, PGC-1?, and even irisin itself [6]
- Involved in lipid and glucose metabolism
- May prevent the development of insulin resistance
- Their secretion may also be affected by the development of muscle insulin resistance [6]
- Decreased serum irisin levels and insulin resistance or diabetes
- Lower circulating irisin levels in type 2 diabetic patients
- Negative correlation with fasting glucose levels
- Decreased circulating irisin levels in the nonobese type 2 diabetic [6]
- Increased circulating irisin levels in extremely obese women
- Correlated with body mass index (BMI) and fat mass
- Adipose tissue as the main source of circulating irisin in such patients
- Obesity may be linked with the development of irisin resistance
- Raise in serum irisin levels in obesity may be a compensatory mechanism, in order to induce lipid metabolism. [6]
- Higher serum irisin levels were found to be correlated with lower HDL cholesterol
- Positively correlated with VLDL, triglycerides, and total cholesterol
- Macrovascular disease typically presented lower serum irisin levels
- Lower serum irisin levels - an independent predictor of macrovascular disease in type 2 diabetic patients [6]
Lacteal junction zippering protects against diet-induced obesity.
- Enterocyte-absorbed lipids are packaged into chylomicrons
- Enter the bloodstream through intestinal lymphatic vessels called lacteals
Preventing lacteal chylomicron uptake
- By inducible endothelial genetic deletion of
- Neuropilin1 (Nrp1)
- Vascular endothelial growth factor receptor 1 (Vegfr1; also known as Flt1)
- Renders mice resistant to diet-induced obesity
- Absence of NRP1 and FLT1 receptors
- increased VEGF-A bioavailability and signaling through VEGFR2 inducing
- Lacteal junction zippering
- Chylomicron malabsorption
- Restoring permeable lacteal junctions by
- VEGFR2
- Vascular endothelial (VE)-cadherin signaling inhibition
- Rescued chylomicron transport in the mutant mice
- Zippering of lacteal junctions by
- Disassembly of cytoskeletal VE-cadherin anchors
- Prevented chylomicron uptake in wild-type mice
- These data suggest that lacteal junctions may be targets for preventing dietary fat uptake.
www.ncbi.nlm.nih.gov/pubmed/30093598
Leandra australis (Cham.) Cogn.
- Pixirica
- Brazil [99]
- Melastomataceae
Leucine
- Branched chain amino acid leucine
- Its metabolites beta-hydroxy-beta-methylbutyrate (HMB) and alpha-ketoisocaproate
- Direct activators of Sirt1
- Leucine allosterically activates Sirt1
- Reducing its Km for NAD+ by >50%
- Enabling Sirt1 activation by nonfasting levels of NAD+
- www.liebertpub.com/doi/10.1089/jmf.2020.0105
- Optimal activation of Sirt1 occurs when leucine is increased
- From fasting levels of 0.10–0.15 mM
- To a concentration of 0.50 mM,35–37
- Clinical dose-ranging studies with oral leucine administration
- This level is achieved with doses of 1–1.5 g leucine
- This level of circulating leucine is clearly achievable
- Exceeds the plasma leucine response to a normal high protein meal
- Readily achieved with supplementation without significant interference from background diet
- 0.5 mM leucine
- Sufficient to optimally activate Sirt1
- Amplify the effects of other Sirt1-AMPK pathway activators without the concomitant mTOR activation
- That may otherwise occur at very high leucine levels (nad 1 mM)
- www.liebertpub.com/doi/10.1089/jmf.2020.0105
Synergie: Leucine + resveratrol + nikotin riboside
Overweight and obese adults
- leucine 1.1 g 2x daily + Sirt1/AMPK pathway activators
- Plasma leucine in the predicted range (0.5 mM)
- Downstream effects consistent with Sirt1 activation
- Increased fat oxidation
- Improved insulin sensitivity
- Reductions in oxidative stress and inflammatory biomarkers
- www.liebertpub.com/doi/10.1089/jmf.2020.0105
Synergie: Leucine + pyridoxal phosphate
- B6 to inhibit de novo lipogenesis
- leucine (1.1 g twice daily) + 15 mg pyridoxine (vitamin B6) twice daily
- Results in stimulation of fat oxidation by 33.6 g/day within 28 days
- 75% increase in circulating adiponectin
- 25–35% decreases in both inflammatory biomarkers
- Tumor necrosis factor-alpha,
- Hs-CRP,
- Oxidative stress biomarkers
leucine-B6 supplement x placebo in subjects on a hypocaloric diet
- leucine-B6 group
- Lost 82% more weight
- 2x as much fat as the placebo group at 12 weeks; at 24 weeks
- leucine-B6 group exhibited
- 55% greater loss of body weight
- 66% greater loss of body fat than the placebo group
- Greater reduction in waist circumference in the leucine-B6 group versus placebo
- Difference was evident at 4 weeks
- Threefold greater loss of waist circumference
- Sustained at the 24-week endpoint twofold greater loss of waist circumference
- Effects were accompanied by significant increases in insulin sensitivity
- Data demonstrate the potential for leucine-B6 combinations in weight management
- www.liebertpub.com/doi/10.1089/jmf.2020.0105
Sildenafil
- Inhibitory effects on phosphodiesterase 5 - in erectile dysfunction
- Low doses (5–10% of current therapeutic doses)
- Activate endothelial nitric oxide synthase (eNOS)
- Increase NO production
- NO also stimulates Sirt1
- Sirt1 deacetylates and activates eNOS in a positive feedback loop
- leucine to synergize with subtherapeutic doses to amplify downstream effects of Sirt1 and AMPK on energy metabolism
- metformin
- Sildenafil
Leucine-metformin combinations
- In diabetes
Leucine, metformin, and sildenafil
- Successful phase 2 clinical trials of a triple combination of nonalcoholic fatty liver disease and obesity
- Presently in further clinical development
Linum usitatissimum L. Linho
- Linaceae
- Linhaça
- Argentina, Bolivia, Canada, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Honduras, Madagascar, Mexico, Nicaragua, Peru, Reino Unido, United States, Uruguay [99]
Luehea divaricata Mart.
- Açoita cavalo
- Bolivia, Brazil, Paraguay [99]
Melanocortin
- Treatment of ob/ob mice with a melanocortin receptor agonist
- Decreased their body weight without affecting their bone mass
www.cell.com/cell/fulltext/S0092-8674(02)01049-8
Morus bombycis Koidz.
- Moraceae
- Amoreira [99]
Myristica fragrans Houtt.
- Noz moscada
- China, El Salvador, Guatemala, Honduras, India, Madagascar, Malaysia, Panama, Taiwan [99]
- Myristicaceae
Orthosiphon stamineus Benth
- Lamiaceae
- Java [99]
Paeonia suffruticosa Andrews
- Árvore peony
- China [99]
- Paeoniaceae
Panax japonicus (Nees) C.A. Mey.
- Ginseng
- Buthan, Burma, China, South Korea, China, India, Japan, Nepal, Thailand, Zambia [99]
- Araliaceae
Paullinia sorbilis Mart.
- Guaraná nI [99]
- Sapindaceae
Phaseolus vulgaris L. Feijao
- Argentnina, Belize, Bolivia, Burma, Canada, China, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Guiana, Honduras, India, Mexico, Puerto Rico [99]
Piper mikanianum (Kunth) Steud.
- Pariparoba
- Argentina, Brazil, Paraguay [99]
Piper nigrum L.
- Pimenta preta
- Belize, Brazil, China, Colombia, Costa Rica, Ecuador, French Guiana, Honduras, India, Peru, Sri Lanka, Venezuela
- Piperaceae
Plantago ovata Forsk.
- Yuan bao che qian, plantain [99]
- Plantaginaceae
Populus balsamifera L.
- Choupo bálsamo
- Bolivia, Canada, Ecuador, United States [99]
Pramlintid a cagrilintid
- Bezpečná, účinná , úspěšně snižují tělesnou hmotnost u pacientů s T2DM
- Následně regulují homeostázu glukózy
- Výsledky mnoha kritických probíhajících studií vrhnou další světlo na klinickou farmakologii a terapeutický potenciál amylinu a jeho analogů
- Kombinace cagrilintidu a semaglutidu CagriSema
- Testována v několika studiích s pacienty s diabetem.
Amylin
- Neuroendokrinní anorexigenní polypeptidový hormon
- Společně s inzulínem vylučován z beta-buněk pankreatu v reakci na konzumaci potravy
- Inhibuje amylin homeostatické a hedonické krmení,
- Navozuje pocit sytosti
- Snižuje tělesnou hmotnost
Rollinia sylvatica Mart.
- Annonaceae
- Pinha, araticum
- Brazil [99]
Rubus coreanus Miq.
- Rosaceae
- Cha tian pao
- China, South Korea, Japan [99]
Salacia reticulata Wight.
- Khotala himbutu [99]
Salix matsudana Koidz.
- Han liu
- Bolivia, China [99]
Scutia buxifolia Reiss.
- Rhamnaceae
- Coronilha, canela de espinho, espinho de touro
- Argentina, Brazil, Paraguay, Uruguay [99]
Senna alexandrina Mill. Sene
- Brazil, Ecuador, India, Mexico, Dominican Republic [99]
Senna corymbosa (Lam.) H.S. Irwin & Barneby
- Sena-do-campo, café-brabo, fedegoso, sena, sena-do-mato
- Argentina, Brazil, United States, Uruguay [99]
Sisyrinchium vaginatum Spreng.
- Iridaceae
- Canchalágua Argentina, Bolivia, Brazil, Ecuador, Guiana, Suriname, Uruguay, Venezuela [99]
Tanacetum vulgare L.
- Catinga-de-mulata, tanaceto, atanásia, erva-de-sao-marcos
- Argentina, Bolivia, Brazil, Canada, Kazakhstan, Chile, China, Colombia, North Korea, South Korea, Costa Rica, Ecuador, El Salvador, United States, Guatemala, Japan, Mexico, Mongolia, Peru, Russia, Venezuela [99]
Taraxacum officinale F.H. Wigg.
- Arnica, dente de leao
- South Africa, Argentina, Canada, Kazakhstan, Chile, China, United States, Guatemala, Madagascar, Panama [99]
Telmisartan
- A human study of 32 patients with type 2 diabetes and metabolic syndrome who received telmisartan demonstrated a significant decline in BMI as well as waist circumference at 6 months compared with baseline
- onlinelibrary.wiley.com/doi/10.1002/oby.22976
Terminalia bellirica (Gaertn.) Roxb. Pi li le,
- Bedda castanheira
- Combretaceae
- Bangladesh, Buthan, Burma, Cambodia, China, Honduras, India, Laos, Nepal, Sri Lanka, Thailand, Vietnam [99]
Acacia mearnsii De Wild.
- Stalk Extraction using water as solvent
- Flavanois (flavan-3-ol e catequins)
- Increased gene expression related to energy expenditure on skeletal muscle
- Decreased fatty acid synthesis In vitro [98]
Achyranthes aspera L.
- Amaranthaceae
- Cola de zorro
- Belize, Bolivia, Brazil, Buthan, Burma, Cambodia, China, Colombia, Costa Rica, Ecuador, United States, Philippines, Gabon, Guatemala, Honduras, India, Jamaica, Laos, Madagascar, Mexico, Nepal, Panama, Peru, Sri Lanka, Thailand, Vietnam [99]
Achyrocline satureioides (Lam.) DC. Marcela do campo
- Argentina, Bolivia, Brazil, Colombia, Ecuador, Guiana, Paraguay, Peru, Uruguay, Venezuela [99]
- Asteraceae
Adenosine receptor
- Stimulate Galpha i
- Inactivation of AC
- Reduces the production of cAMP (=stop lipolýzy)
- Attenuation of the lipolytic response [7]
Adiponektin
- Beneficial effects on insulin resistance and metabolic disorders
- Increase in fatty acid oxidation in muscle and liver.
- 5'-AMP-activated protein kinase (AMPK)
- P38 mitogen-activated protein kinase (MAPK)
- Are involved in the activation of peroxisome proliferator-activated receptor (PPAR)alpha
- By adiponectin in muscle cells
- Adiponectin increases the
- Transcriptional activity of PPARalpha
- The expression of its target genes, including
- ACO, CPT1, and FABP3 in C2C12 myotubes
- Suppressed by the overexpression of a dominant-negative form of AMPK.
- Chemical inhibitors of AMPK and p38 MAPK
- Potently repressed fatty acid oxidation and the induction of PPARalpha target gene expression by adiponectin.
- AraA
- An AMPK inhibitor
- Prevented the activation of p38 MAPK
- SB203580
- A p38 MAPK inhibitor
- Did not affect AMPK activation
- P38 MAPK is a downstream signaling factor of AMPK
- Results suggest that adiponectin stimulates fatty acid oxidation in muscle cells
- By the sequential activation of AMPK, p38 MAPK, and PPARalpha.
- www.ncbi.nlm.nih.gov/pubmed/16936205
Adiponutrin - Adpn - Pnpla3 - acylglycerol-O-acyltransferase - calcium-independent phospholipase A2 epsilon - iPLA2-epsilon
- T3 stimulate adiponutrin
- Triacylglycerol lipase
- Strongly upregulated by T3 in rat and human white and brown adipocytes (Calvo and Obregon, 2009) [80]
- Lipase with double action
- Lipase involved the hydrolysis of triacylglycerol
- In acyl-CoA transacylation of acyl-glycerols
- Involved in lipid homeostasis [80]
Adipose triglyceride lipase (ATGL)
- no specificity for the hydrolysis of MG, cholesterol esters, or retinyl esters
- Hydrolytic function is not restricted to the catabolism of lipid droplets in adipose tissue
- ATGL initiates lipolysis
- By removing the first FA from TG to, in turn, produce DG [7]
- HSL generates an additional FA from DG and MG to produce glycerol
- Phosphorylation of lipases
- Plays a central role in the regulation of enzyme activity
- ATGL protein are significantly increased in human skeletal muscle by fyzicka aktivita [7]
- Facilitates hormone-stimulated lipolysis in white adipocytes in mammals [7]
Adipose triglyceride lipase
Aegle marmelos (L.) Correa
- Reduction of triglyceride
- Red. of cholesterol levels
- Lipid metabolism modulation
- In vivo/in vitro
- Leaf
- Accelerated extraction using as solvents n-ethanol, hexane, n-butanol and dimethyl carbonate Cumarins [98]
- Rutaceae
- Fruta de bael
- Buthan, Cambodia, China, Honduras, India, Laos, Suriname, Vietnam [99]
Ajoene+CLA and vitamin D+genistein
- CLA
- Enhanced ajoene-induced apoptosis in mature 3T3-L1 adipocytes
- By synergistically increasing the expression of several proapoptotic factors
- Genistein
Akebia quinata (Houtt.) Decne
- Fruit
- In vitro anti-obesity effects on 3T3-1 pre-adipocyte cells
- Reflux extraction using ethanol at 70° as solvent
- Phenolic compounds [98]
Alpha 2-adrenergic receptor
- Stimulate Galpha i
- Inactivation of AC
- Reduces the production of cAMP (=stop lipolýzy)
- Attenuation of the lipolytic response [7]
Androgeny
- Stimulatory effect on lipolysis
- Impairment of adipocyte differentiation
- Zhoršení insulin signalling
- Regulation of body fat distribution
- Direct effects on adipocyte differentiation in a depot-specific manner
- Modulation of adipocyte size and fat compartment expansion
- Insulin signalling
- Lipid metabolism
- Fatty acid uptake
- Adipokine production
- Effects are frequently gender-specific
- testosterone regulates the expression of genes in glucose metabolism in men
- Promote insulin sensitivity
Androgen excess In men
- High serum testosterone associated with insulin sensitivity [51]
- Testosterone action in skeletal muscle
- Promotes insulin sensitivity in males [51]
Annona montana Macfad.
- Annonaceae
- Jaca-de-pobre, falsa graviola
- Bolivia, Brazil, China, Costa Rica, Ecuador, United States, Guiana, French Guiana, Honduras, Panama, Peru, Suriname, Venezuela [99]
Anorektické účinky
AMK s rozvětveným řetězcem
- Izolovaný nedostatek AMK s rozvětveným řetězcem
- Múže podporovat podmíněnou chuťovou averzi (Gietzen and Magrum, 2001). [1]
Amylin
- Působení jako na dopaminové receptory
- Periferní mediátory regulace příjmu potravy
- Vylučován spolu s inzulinem
- Indukuje akutně sytost působením na receptory pro dopamin D2 (Lutz a kol., 2001) [1]
Apolipoprotein IV
- Produkce spojena s rozsahem absorpce tuku (běžná součást chylomikronů)
- Potlačuje chuť k jídlu (Tso a kol., 2001) [1]
Beta-adrenergní agonisté
- Sibutramin [1]
D2 receptory - agonisté
Enterostatin
- Proteolýzou pankreatické kolipázy
- Pentapeptid (Val-Pro-Asp-Pro-Arg)
- Potlačuje chuť k jídlu
- Zvyšuje sekreci inzulinu (Bouras a kol., 1995) [1]
Gastrinový inhibiční peptid
Gastrin uvolňující peptid (GRP)
- Souvisí s bombesinem [1]
Glukagonu podobné peptidy 1 (GLP-1) a 2
- Reakce na MK a cukry ve stravě
- Ileum
- Infuze GLP-1
- Zvýšení potenciálu nasycení u fixní kalorické zátěže
- Vedou ke snížení příjmu potravy podle libosti
Histamin produkující neurony
Cholecystokinin (CCK)
- Hraje hlavní roli v regulaci chuti k jídlu
- Omezením množství jídla
- Poskytováním pocitu plnosti
- Vylučován endokrinními buňkami duodena
- Moduluje i dlouhodobý příjem potravy [1]
- Účinky tuku na chuť k jídlu souvisely s odpovědí CCK
- Zpoždění vyprazdňování žaludku [2]
Cholecystokyninové receptory CCK-A
- V tenkém střevě
- Ukončují příjem potravy (Moran, 2000) [1]
Cholecystokyninové receptory CCK-B
- CCK nepůsobí přímo na CCK-B receptory v mozku
Chuť a čich - porucha vnímání
- Ve vyšším věku
- Může snížit adekvátní chuť k jídlu
- Významnou překážku pro normální jídlení chování (Schiffman and Graham, 2000) [1]
Katecholaminy produkující neurony
Laktát
- Zpomaluje příjem potravy [1]
Mastné kyseliny - MK
- Důležitým vlastnostmi ovlivňující expresi chuti k jídlu u člověka (via CCK, GLP-1)
- Délka řetězce
- C12 účinnější než C10 (Feltrin a kol.,2004)
- Stupeň saturace
- PUFA 18 silnější než MUFA 18, SFA 18 (Lawton a kol.,2000)
- CCK signalizace úzce souvisí s transportem chylomikronů
- Pouze MK 12C a více indukují CCK [2]
Melanokortin
- Produkován v post-translačním procesu (Pritchard a kol., 2002) proopiomelanokortinu (POMC), který je také prekurzorem
- Alfa, beta, gamma-MSH (melanocyty stimulujícího hormonu)
- ACTH (adrenokortikotropního hormonu) [1]
Melanokortinové neurony
- Produkují melanokortin (Schwartz a Morton, 2002)
- Inhibovány
- Leptinem
- Inzulinem
- Informacemi z NPY/AgRP neuronů [1]
Melanokortinové receptory
- Vazba melanokorinu v ncl. arcuatus [1]
- Receptor 4 (Mc4r) na hypotalamických neuronech
- Inhibuje chuť k jídlu [1]
Metabolity trávení
- Zpětnovazebnou regulaci omezením příjmu potravy [1]
N. Vagus
- Žaludek a střevo
- Receptory napnutí
- Chemoreceptory [1]
- Signalizují lokální nasycení do mozku
- Aferentní vlákna n. vagus mohou přenášet signály z GIT až do CNS [1]
NPY/AgRP neurony podporující chuť
- Inhibovány
Proteiny
- P-ratio jedinců před redukčním programem (Minesota study)
Pyruvát
- Zpomaluje příjem potravy [1]
PYY3-36 aktivita
- Typ NPY receptoru Y2R
- Reaguje jak na intaktní NPY tak na fragmenty, jako e PYY3-36
- Snižuje chuť k jídlu [1]
Serotonin
- Příjem potravy stimuluje uvolnění serotoninu těmito neurony a tím indukuje pocit nasycení [1]
Serotoninergní medikace - zvyšující dostupnost serotoninu
- Dexfenfluramin aj.
- Indukují úbytek tělesné hmotnosti
- Plicní hypertenze
- Porucha srdečních chlopní (Michelakis and Weir, 2001) [1]
Tuk snědený
- Uvolnění CCK - omezuje příjem potravy (Moran, 2000)
- Sekreci enzymů a šťáv pankreatu
- Lipáza a kolipáza
- Normální trávení TG na FFA podmínkou pro vylití CCK a GLP-1
- Cholesterolových esterů
- Absorpce FFA - chylomikrony
- ApoAIV - potlačuje chuť k jídlu, zvláště tuku (Tso a kol., 2001) [1]
- Proteázy tráví kolipázu
- Enterostatin - silný inhibitor chuti k jídlu, zvláště pro tuk
- Indukuje sekreci inzulinu [1]
Literatura:
[1] KOHLMEIER M., NUTRIENT METABOLISM. ACADEMIC PRESS, LONDON, 2003, 826 PP. ISBN 0-12-417762-X, STR. 25-30. Regulace příjmu potravy. Chuť k jídlu. URL < appetitestop.cz/pdf/regulace.pdf >.
[2] Hughes.pdf (application/pdf objekt). URL < appetitestop.cz/pdf/Hughes.pdf >.
Anorexigenní vlivy
Podnět sytosti
- Z analyticko-regulačního centra v hypotalamu
- Z okolních jader
- Do pocitu potěšení v limbickém systému
- Do orbitofrontální korové oblasti
- Potěšení z jídla
- Stav nálady [5]
Leptin
- Product of the ob gene
Inzulín
- In the CNS reduce food intake [79]
Glucose
Free fatty acids
- Important role as signals
- Reflecting energy homeostasis
- In specific hypothalamic neuronal circuits [79]
ANP (NPPA)
- Affect brown adipocyte activation
- + recruitment of BAT
- Promising for the development of new anti-obesity drugs [77]
L-arginine
- Nitrogenous precursor of nitric oxide
- Regulates multiple metabolic pathways
- Arginine stimulates
- Lipolysis
- Expression of key genes responsible for activation of fatty acid oxidation to CO2 and water
- Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha)
- mitochondrial biogenesis
- Growth of brown adipose tissue growth [48]
- Arginine regulates
- Adipocyte-muscle crosstalk
- Energy partitioning
- Via the secretion of cytokines and hormones [48]
- Enhances AMP-activated protein kinase (AMPK) expression and activity
- Modulating lipid metabolism and energy balance toward the loss of triacylglycerols
- Dietary supplementation with arginine
- Effectively reduces white adipose tissue in
- Zucker diabetic fatty rats
- Diet-induced obese rats
- Growing-finishing pigs
- Obese patients with type II diabetes [48]
- Arginine can be used
- To prevent and treat adiposity and the associated metabolic syndrome [48]
Aromatáza
- Catalyzes the conversion of androgen to estrogen
- Mice with knocked out aromatase (ARKO) became obese when fed the same amounts as normal mice [2]
Artemisia princeps Pamp. Kui hao,
- Yomogi
- China, North Korea, South Korea, Japan [99]
Artemisia princeps Pamp.
- Leaf Reflux extraction using ethanol at 70° as solvent
- Phenolic compounds [98]
Asparagus Officinalis
ATGL - desnutrin - Pnpla2
- Lipáza
- (Ahmadian et al., 2010, 2011) [80]
bFGF stimulation
- Promoted the survival of the BAT
Bariatrická redukce hmotnosti před otěhotněním
- Children born after maternal weight loss
- Lower risk for obesity than do their siblings born before maternal weight loss (Kral et al., 2006)[1]
- “metabolic imprinting” of body weight regulation (Waterland and Garza, 1999; Waterland, 2005) [1]
Basic fibroblast growth factor (bFGF)
- Stimulation of the cells also results in Erk activation
- Similar to the effect of NE
- NE caused transient Erk activation
- BFGF caused sustained Erk activation
- The phosphorylation of Erk1/2 was sustained for more than 4 h following bFGF stimulation [86]
- May contribute to the enlargement of the tissue
- NE increases bFGF messenger RNA (mRNA) levels
Increased BAT activity
- Associated to lean phenotypes
Stimulation of pre-existing brown adipocytes within white adipose depots
Beta 1 adrenergic agonists
- Increases in DNA synthesis were confirmed in primary cultures of brown preadipocytes [88]
Termogeneze
- Beta 3-AR has been linked to thermogenesis in human skeletal muscles
- Studies showing it to be responsible for over 40% of ephedrine-induced thermogenesis
en.wikipedia.org/wiki/Beta3-adrenergic_agonist
Beta 3 adrenergic agonists
- Induce UCP1 in muscle
- Provides a mechanism against weight gain (Almind et al., 2007)
Beta 3-adrenergic stimulation of thermogenesis in BAT
- Exposure to cold
- Catecholamines
- Augmentation of thyroid function
- Modulation of PPAR gamma
- Transcription factors of the C/EBP family
- PPAR? co-activator PRDM16
- COX-2-driven expression of UCP1
- Stimulation of the vanilloid subfamily receptor TRPV1 by
- capsaicin
- Monoacylglycerols
- BMP7 or its analogs
- Cannabinoid receptor antagonists
- Melanogenesis modulating agents
- Manipulating one or more of these pathways
- May provide a solution to the problem of harnessing brown fat's thermogenic potential [46]
Beta 1-, beta 2-, and beta 3-adrenergic receptors (beta-ARs)
- Stimulation of G-protein coupled receptors (GPCRs)
- GDP release
- GTP binding
- Activation of adenylyl cyclase (AC)
- Production of cAMP + (=aktivace lipolýzy)
- Increased intracellular cAMP level
- Phosphorylates and activates cAMP-dependent protein kinase A (PKA)
- Phosphorylates hormone-sensitive lipase (HSL) [7]
- CAMP-dependent protein kinase (PKA) phosphorylation of HSL at:
- Ser563
- Ser659
- Ser660 [7]
- Enhances its enzymatic activity
- Extracellular-regulated kinase (ERK)
- Induces the phosphorylation of HSL at Ser600 in 3T3-L1 adipocytes [7]
- Phosphorylated HSL
- Activates the hydrolysis of TG in adipocytes
- Translocation of HSL from the cytoplasm to the surface of lipid droplets [7]
Alfa-AR-cAMP production
- Alpha-2-ARs modulate lipolysis at rest [7]
- Complete activation of lipolysis in white adipocytes [7]
- Only when catecholamines were in the presence of an alpha2-AR antagonist in human [7]
- Alpha-2-antilipolytic component counteracting the beta-AR-mediated lipolysis [7]
- Well known as the “?alpha/beta-adrenergic balance”
beta-AR-cAMP production
- Beta-ARs modulate lipolysis during physical exercise [7]
- Even if ?2/beta-adrenergic balance exists in human white adipocytes [7]
- Number of ?2-ARs in jerboa, dormouse, and rat is lower than that in humans [7]
Bilberries
- Show significant decreases in body weight in studies
- Significant decrease in waist and hip circumferences [96]
Bioavailable testosterone
- Albumin-bound fraction and free testosterone
- Positively related to
- Muscle strength
- Total body bone mineral density [52]
- Negatively related to
- fat mass in healthy elderly men [52]
Bisphenol A diglycidyl ether (BADGE)
- Time-depended increase in expression of
- adiponectin
- Lipid oxidative enzymes
- Reduced body weight
- Reduced epididymal adipose tissue weight
- Marked reduction in the number of fatty droplets in the liver [1]
Bitter melon (Momordica charantia)
- Vegetables in South China
- Feeding diet-induced obese rats with bitter melon juice
- Reduced adiposity
- Increased lipid oxidative enzyme activities
- Increased uncoupling protein expression
- Suppression of the visceral fat accumulation
- Inhibition of adipocyte hypertrophy
- Down regulation of expressions of lipogenic genes in the adipose [1]
- Phytoestrogens and other polyphenolic chemicals may be responsible [1]
Black Chinese tea - Pu-Erh tea - Pu’er tea
- Show significant decreases in body weight in studies
- Seem to have satisfactory anti-obesity effects [96]
- Significant decrease in body fat [96]
- Significant decrease in waist and hip circumferences [96]
- Decreased the waist-hip ratio significantly [96]
- Kubota et al 2011, Pre-obese male [n?=?36] Black Chinese [Pu-Erh] tea , double blind
- 333 mg before each of 3 daily meal
- 12 wk
- I: extract C: control
- Decrease in BW and BMI
- Sig. effects in reducing the mean WC and visceral fat values
- No adverse effects <0.05 [96]
- Chu et al 2011 , Human with Metsyn [n?=?90] Pu'er tea RCT , double blind
- 4 Cap each time
- Twice per d
- 3 mo
- I: extract C: placebo
- Decrease in
- BMI
- Waist-hip ratio
- Fasting and 2 h postprandial blood glucose
- Serum TC, TG, LDL-chol and apolipoprotein B-100 [96]
Blueberry
- An extract of Blueberry Bioactives
- A significant decrease in appetite
BMP8B
- Affect brown adipocyte activation
- + recruitment of BAT
- Promising for the development of new anti-obesity drugs [77]
Brite adipocytes
- Presence and activation
- Associated to lean phenotypes
Browning
- White-to-brown transdifferentiation
- Mature adipocytes undergo genome reprogramming
- Turn into a different cell type
- Reversible
- Essential to meet increased heat production requirements during chronic cold exposure
- Chronic cold exposition
- Branching of noradrenergic parenchymal fibres
- Increasing BAT sympathetic innervation
- Beta3-adrenoceptors (AR)
- Specifically expressed by brown adipocytes
- By noradrenaline
- Drive brown adipocyte thermogenic activation
- White-to-brown transdifferentiation
- Knockout beta3-AR mice
- Do not undergo browning [77]
cAMP aktivace
- Hormonal stimulated lipolysis
- By activation of cyclic AMP-dependent protein kinase (PKA)
- Phosphorylates hormone-sensitive lipase (HSL)
- Increases adipocyte lipolysis
CGI-58
- Alpha/ß hydrolase domain-containing protein 5 (ABHD5)
- Increase the TG hydrolase activity of ATGL
- Direct interaction with ATGL proteins
- Ability to be associated with perilipin 1
- Involved in the organization and regulation of lipolytic effector interactions
- Localizes on the lipid droplet surfaces with perilipin 1
- ATGL exists predominantly within the cytoplasm
- Attenuation of the interaction of ATGL with CGI-58
Caffeine
Camellia Sinensis
- Show significant decreases in body weight in studies
- Seem to have satisfactory anti-obesity effects [96]
- Basu et al 2011 [13] Obese with Metsyn [n?=?35]
- Camellia Sinensis RCT 4 cups/d green tea
- Or 2cap and 4 cups water/d/8 wk
- I: green tea or extract
- C: water
- Sig. decrease in BW and BMI
- A decreasing trend In LDL-chol and LDL/HDL ratio [96]
Camellia thea Link
- Reduction of triglyceride levels
- In vivo/in vitro
- Leaf Extraction by maceration using water as solvent
- Phenolic compounds
- Serum triglycerides and non-esterified fatty acids
- Flavanois (catechins)
- Alkaloids (cafeinne) [98]
Cellular cyclic AMP
- Zvýšení
- Potlačení syntézy MK během minut
- Changes in glucose transport
- Pokles pyruvate kinase akt.
- Pokles pyruvate dehydrogenase akt.
- Changes in phosphorylation of the alpha subunits [4]
- Pokles acetyl-CoA carboxylase akt.
Increases in the intracellular cAMP level
- Induce apoptosis or protect cells from apoptosis
- Depending on the cell type and the circumstances
- In brown adipocytes promotes the cell survival [76]
- NE, alpha 1-, and beta-receptor agonists
- Activated the Erk cascade in mouse brown adipocytes
- Dependent on the influx of extracellular Ca2+
- Increases cAMP levels [76]
- Beta-receptor-stimulated Erk activation
- Mediated by cAMP/PKA
- Activates the Erk cascade through a B-Raf and Rap1-dependent pathway
- Brown adipocytes express both Rap1 and B-Raf
- MEK signaling pathway [76]
Capsinoides
- Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that
- Increase energy expenditure
- Decrease body fat
- Single oral ingestion of capsinoids
- Increases energy expenditure in human individuals with metabolically active BAT
- But not those without it [12]
- Capsinoids activate BAT
- Increase energy expenditure [12]
- Human BAT may be inducible
- Prolonged ingestion of capsinoids would recruit active BAT
- Thereby increase energy expenditure and decrease body fat [12]
- Role of capsaicin as an anti-obesity agent
- Intestinal mucosal afferent nerves
- Appear to play a role in controlling adipose tissue distribution between visceral and subcutaneous sites
- Activation of the transient receptor potential vanilloid-1 channels by capsaicin
- Prevents adipogenesis
- A neurogenic mechanism
- Modulates the regulation of fat metabolism
- By transient receptor potential vanilloid-1-sensitive sensory nerves
- A neural pathway enables the selective activation of the central network
- Regulates brown adipose tissue sympathetic nerve activity
- In response to a specific stimulation of gastrointestinal transient receptor potential channels
- Dietary capsaicin
- Reduces metabolic dysregulation in obese/diabetic mice
- By enhancing expression of adiponectin and its receptor
- In adipose tissue and liver
- Dual action on
- Peroxisome proliferator-activated receptor alpha
- Transient receptor potential vanilloid-1 expression/activation [12]
- Local desensitization of the abdominal capsaicin-sensitive fibers
- Oslabuje the hypometabolic adaptation to food deprivation
- Thermogenesis and lipid metabolism-related proteins
- Altered upon capsaicin treatment in white adipose tissue [12]
- Capsaicin
- Induces apoptosis
- Inhibits adipogenesis in preadipocytes and adipocytes [12]
- Epidemiologic data show that consumption of foods containing capsaicin
- Is associated with a lower prevalence of obesity [12]
- Clinical evidence supports a role of capsaicin as an anti-obesity agent
- Oral and gastrointestinal exposure to capsaicin
- Increase satiety
- Reduce energy and fat intake [12]
- Capsaicin consumption 1 h before low intensity exercise
- Valuable supplement for the treatment of individuals with hyperlipidemia and/or obesity
- Improves lipolysis [12]
- Associated with an increase in fat oxidation that is nearly significant
- Two common genetic variants
- May be predictors of response [30]
- Snitker et al 2009, Healthy [n?=?80] Capsinoids double blind
- 6 mg/d/12 wk powder
- Decrease in abdominal adiposity [96]
Carica papaya L. Mamao
- Argentina, Bahamas, Belize, Bolivia, Brazil, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, United States, Gabon, Guatemala, Guiana, French Guiana, Haiti, Honduras, Cayman Islands, Virgin Islands, Jamaica, Madagascar, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican Republic, Suriname, Trinidad and Tobago, Venezuela [99]
- Caricaceae
Carica papaya L.
- Leaf Extraction by maceration using methanol as solvent
- Suppression of appetite stimulus signals in the hypothalamus
- In vitro
- Saponins
- Fruit Decoction extraction using water as the solvent
- Reduced levels of triglycerides, LDL-C E VLDL-C
- In vivo/in vitro
- Alkaloids, saponins, tannins, anthraquinones, flavonoids (antocianidinas) [98]
Semen Cassiae
- Significant decrease in body fat [96]
Catechin enriched green tea
- Significant decrease in body weight [96]
Catechin enriched green tea
- Show significant decreases in body weight in studies
- Significant decrease in body fat [96]
- Significant decrease in waist and hip circumferences [96]
Catecholamines
- Main factor involved in the control of lipolysis
- But antilipolytic effect of insulin is predominant
- Catecholamines exert their effect when insulin level is low
- Sympathetic nervous system
- Is the main driver for adipose tissues lipolysis [78]
- Stimulation of sympathetic nerves
- Has no main effect on glucose uptake, utilization and lipogenesis in WAT [78]
- Brown adipose tissue activity
- Mainly under the control of the sympathetic system
- Binding of norepinephrine on beta adrenoceptor
- Induces lipolysis
- Activity of UCP
- Enhanced thermogenesis [78]
- Stimulation of ß-adrenoceptor
- Decreases the release of leptin
- Posttranslational mechanism [78]
- Up-regulation of pro-inflammatory cytokines
- TNFa and IL6
- Down-regulation of adiponectin
- May contribute to the pathogenesis of catecholamine-induced insulin resistance [78]
- May mediate short-term decrease in plasma leptin
- Within hours of fasting and cold exposure [78]
CB1 receptor antagonists
- Decrease food intake
- Induce significant weight loss
- Anxiety and depression
Cichorium intybus L.
- Chicória
- Canada, Chile, China, El Salvador, United States, Guatemala, Honduras, Madagascar, Mexico, Panama, Venezuela [99]
- Leaf Extraction using hexane, ethyl acetate and methanol as the solvent
- Tannins [98]
Cirazoline
- Promoted the survival of the BAT
Cissus Quadrangularis (CQ)
Comparative gene identification-58 (CGI-58) [7]
- Facilitates hormone-stimulated lipolysis in white adipocytes in mammals [7]
CPT-1
Crocus Sativus L
- Show significant decreases in body weight in studies [96]
- Gout et al 2010 [14] Mildly over wt. women [n?=?60]
- Satiereal, [Crocus sativus L extract] RCT [double blind]
- 176.5 mg/d/8 wk
- I: extract
- C: placebo
- A Sig. BW reduction
- Decrease in mean snacking frequency [96]
Cucurbita moschata D.
- Stalk Extraction by maceration using water as solvent
- Terpenes
- In vivo/in vitro [98]
Cucurbita moschata Duchesne.
- Cucurbitaceae
-Bolivia, Brazil, Colombia, Costa Rica, United States, Ecuador, Guiana, French Guiana, Honduras, Mexico, Panama, Suriname, Venezuela [99]
Curcumin
- Down-regulate the expression of key genes involved in adipocyte differentiation including
- C/EBP
- PPAR
- AP2
- Induce G0/G1 and G2/M cell cycle arrest
- Apoptosis of adipocytes
- + of DNA fragmentation
- + caspase-3 activation
- Inactivated NF-kappa B and MAPK
- Increased curcumin content in adipocytes
- Positively correlated with enhanced anti-adipogenic ability
Cyclic AMP-dependent protein kinase (PKA)
Cyperus rotundus L. Tiririca
- Junça
- Afghanistan, Argentina, Australia, Belize, Bolivia, Brazil, Buthan, Burma, Kazakhstan, Chile, China, Colombia, North Korea, South Korea, Costa Rica, Ecuador, El Salvador, United States, Philippines, Gabon, Guatemala, Guiana, French Guiana, Honduras, India, Japan, Madagascar, Malaysia, Mexico, Mongolia, Nicaragua, Panama, Papua New Guinea, Pakistan, Paraguay, Peru, Sri Lanka, Suriname, Thailand, Venezuela [99]
- Cyperaceae
D2 deiodinases
- Participates in the formation of BAT (Carmona et al., 2002)
- With low UCP1 mRNA, D2 activity, and low mitochondriogenesis
- Implicated in the process of lipogenesis under adrenergic stimuli (Bianco et al., 1998)
- D2 is a marker of BAT activation (thermogenesis).
D2 knockout mice
- Hyper-adrenergic stimulation compensatory for the lack of T3 production in BAT
- Lipogenesis is not providing the FFA levels required during cold exposure
- Impaired adaptive thermogenesis (Christoffolete et al., 2004)
Debese
- Showed a reduction in triceps skin folds in a trial [96]
- Significant decrease in waist and hip circumferences [96]
- Rehman Riaz et al 2011, Obese [ n?=?100] Debese
- 2 yr
- I: Debese x Sibutramine
- Decrease in BMI, WC
- Reduction of triceps skin fold [96]
Desensitization capsaicin-sensitive fibers
- Local desensitization of the abdominal capsaicin-sensitive fibers
- Oslabuje the hypometabolic adaptation to food deprivation [12]
Dexfenfluramine (Redux)
- Suppress appetite
- Mainly by increasing release of serotonin by the cells
- Withdrawn from the market in September 1997
- Association with pulmonary hypertension
- Damage to the heart valves
Differentiation of brown fat adipocytes de novo
- Preadipocyte development
- Documented after administration of beta1-AR agonists
Dioctanoylglycerol
- Treatment of adipocytes with
- Activates ERK
- Increases lipolysis [77]
Dioscorea nipponica M.
- Suppression of increased triglyceride level in the blood In vivo
- Root Extraction by maceration using methanol as solvent
- Saponins [98]
Drospirenone (DRSP)
- A progestogen
- Modest antiandrogenic activity
- Widely used for contraception
- Strongly inhibits adipose differentiation both in murine (3T3-L1) as well as in human preadipocytes ex vivo
- Powerful antagonist of the mineralocorticoid receptor (MR)
- Pivotal factor for the induction of adipogenesis [69]
- Antiadipogenic effect of DRSP relies on specific antagonism on the MR
- Blunted in presence of testosterone
- Chronickým užíváním androgenů
- Increased levels of AR may bind DRSP as an AR antagonist
- Overall availability of DRSP as an anti-MR could result reduced [69]
Ephedra
Epigallocatechin gallate and green tea extract
- Dried leaves of the Camellia Sinensis plant.
- Fermented black tea
- Partially fermented oolong tea [20]
- Green tea is a non-fermented tea
- Direct drying of fresh green tea leaves
- By hot steam and air [20]
- Polyphenol oxidase is inactivated
- Polyphenols are preserved
- Green tea contains the highest amount of green tea catechins
- Major polyphenols in green tea
- Cca 35% of its total dry weight [20]
- 2-gram bag of green tea contains
- Cca 500 mg of green tea catechins
- Most abundant green tea catechins are
- (-)-epigallocatechin gallate (EGCG)
- Cca 68–69% of green tea catechins [20]
- (-)-epigallocatechin (EGC)
- Circa 15–18%
- (-)-epicatechin gallate (ECG)
- Circa 5–6%
- (-)-epicatechin (EC)
- Circa 2–5% [20]
- The anti-obesity potential of green tea catechins
- Particularly EGCG
- Inhibiting preadipocyte differentiation
- Decreasing adipocyte proliferation
- Inducing adipocyte apoptosis
- Suppressing lipogenesis
- Promoting lipolysis and fatty acid beta (ß)-oxidation [20]
- EGCG (10–100 µM) and with lower potencies, EC and EGC
- Induce dose- and time- dependent
- Decrease in adipocyte viability
- Cell cycle arrest at the G0/G1 phase [20]
- Lower concentrations (0–10 µM) EGCG
- Induced in a dose-dependent manner in mature 3T3-L1 adipocytes
- G2/M growth arrest [20]
- EGCG (0–400 µM) and less potently ECG, EGC and other catechins
- Induce apoptosis in murine 3T3-L1 preadipocyte and mature 3T3-L1 adipocytes
- Increased caspase-3 activity [20]
- EGCG (0.5–10 µM)
- Inhibits preadipocyte differentiation
- At higher concentrations (50–200 µM)
- Inhibits in a dose- and time-dependent manner
- Cellular triglyceride accumulation in adipocytes [20]
- EGCG-mediated suppression of adipocyte differentiation
- Impact on genes playing crucial roles in adipocyte differentiation - two key regulators of adipocyte differentiation
- Peroxisome proliferator activator receptor (PPAR )
- CCAAT/enhancer binding protein (C/EBP ) [20]
- Ovlivnění další řady genů
- Acetyl-coenzyme A carboxylase (ACC)
- Converts acetyl-CoA to malonyl-CoA, a building block for fatty acid synthesis
- Inhibitor for fatty acid oxidation
- Transcriptional factor sterol regulatory element-binding protein 1c (SREBP-1c)
- Enhances lipogenesis and adipogenesis [20]
- EGCG’s effect on adipocyte differentiation is accompanied by
- GTC
- Decrease food intake
- Increased energy expenditure
- Up-regulating uncoupled proteins [20]
- EGCG up-regulate
- Lipolysis
- Thermogenesis
- Glycerol release
- Expression of hormone sensitive lipase
- Carnitine palmitoyltransferase-1 (CPT-1)
- Involved in fatty acid ß-oxidation in 3T3-L1 cells [20]
- MRNA levels of uncoupling protein (UCP)-2
- Reduced expression of resistin
- An adipocyte-derived inflammatory adipokine
- Associated with insulin resistance
- Increased risk of cardiovascular disease (CVD)
- EGCG-mediated anti-inflammatory response
- Insulin sensitization [20]
- 3T3-L1 adipocytes incubation with 100 µM EGCG for 3 hours
- Decreased
- MRNA
- protein levels of resistin by 50% [20]
- Beneficial effects of EGCG or GTE on obesity-related parameters including
- Decreased BW
- Adipose mass
- Total lipids
- cholesterol
- Triglyceride (TG)
- Triacylglycerol (TAG) in liver and plasma
- Improved glucose homeostasis
- Increased glucose tolerance
- Decreased serum glucose
- Decreased insulin resistance
- Decreased homeostasis model assessment-insulin resistance (HOMA-IR) [20]
- Suppressing dietary fat absorption
- Enhancing fat oxidation in adipose tissue and skeletal muscle
- Increasing glucose utilization
- Decreasing de novo lipogenesis
- Antioxidant and singlet oxygen quencher
- Inhibiting the destructive effects of ROS
- Suppressing inflammation in the development of obesity [20]
- Catechin or an EGCG-caffeine mixture contained in green tea had a small effect on weight loss and weight maintenance
- Green tea had no significant effect on the maintenance of weight loss
- Discrepancies among these clinical studies employing green tea
- Varieties of study designs
- Uncontrolled design, RCT, crossover
- Length of study (24 hours - 24 weeks)
- Age and gender of subjects, the ethnicity of subjects
- Formulations of green tea supplement (EGCG, GTC, GTE)
- Presence or absence of weight control factors (caffeine, exercise, low-caloric diet), etc. [20]
- Dietary supplementation with EGCG or GTE
- Potentially viable nutritional strategy for the prevention of obesity
- Low bioavailability of GTC along with potential confounders
- Inconsistent outcome of human studies [20]
- EGCG is incorporated into cytoplasma
- Further transported into nuclei in L-929 cells [20]
- Uptake of EGCG by HT-29 cells is via a passive diffusion process
- EGCG can bind on its receptor
- 67 kDa laminin receptor on cancer cells
- Activate subsequent signaling molecules and anti-cancer activities including
- Decreasing cell viability
- Inducing apoptosis
- Altering intracellular Ca2+ [20]
- 67 kDa laminin receptor was expressed in 3T3-L1 and C3H10T1/2 adipocytes
- EGCG binding to this receptor
- Could inhibit insulin stimulation of adipocyte glucose uptake
- Blocked by the receptor antibody [20]
- 3T3-L1 cells
- Do not express adequate levels of certain adipocyte-specific genes
- Some other metabolic genes not at the degree expressed in whole adipose tissue
- These cells do not represent
- Complex and diverse cell type populations
- Microvascular system
- Extracellular matrix of the whole adipose tissue [20]
- Thielecke et al 2010, Obese male [n?=?10]
Erk1/2
- Critical role in promoting NE- and bFGF-dependent survival of brown adipocytes [63]
Estrogen replacement therapy (ERT)
- Decreases WAT (Wade et al 1985) [1]
- Syrian hamsters with estrogens
- Decreases in body weight and fat without affecting food intake
- Higher Myocardial fatty acid utilization in postmenopausal women taking E2 [1]
Estrogenní receptor alfa
- E2/ER alfa signaling is critical in female and male WAT and that obesity
- Involves a mechanism of reduced energy expenditure [2]
- E2 effects on adipose tissue are predominately through ER-alfa [2]
- Ovariektomie in 8-week old female Wistar rats induced hyperphagia
- Effects were fully reversed by subcutaneous E2 replacement [2]
- Membrane pool of ER-alfa is likely not involved in E2 regulation of body weight and obesity [2]
- Nuclear and mitochondrial pools of ER-alfa may be responsible for E2 regulation of body weight and obesity [2]
- Detected in mitochondria of
- HepG2
- MCF-7 cells
- Rat cerebral blood vessels [1]
Estrogen receptor alfa knocked out (alfa-ERKO) mice
- Adipocyte hyperplasia/hypertrophy
- Vzestup hmotnosti
- Insulin resistance
- Glucose intolerance [1]
- Reduced energy expenditure in both sexes [2]
- 10-fold increase in E2 [2]
- Persistent / increased E2 signaling through ER-beta [2]
- Obesity factor in alfa-ERKO mice ? [2]
- Strong staining for ER-beta in adipose tissue [2]
- Ovariectomized (Ovx) alfa-ERKO mice
- Removing E2/ER-beta signaling in alfa-ERKO mice by ovariectomy
- Poklesla hmotnost proti alfa-ERCO
- 45% decreases in bodyweight and adipocyte circumference [2]
- Nižší hladiny glukózy před i po gluk. inj. [2]s
- Nižší hladiny inzulínu
- E2 replacement (rušení účinků ovariektomie)
- Expression of ER-alfa functional domain in plasma membrane in alfa-ERKO mice did not prevent from developing obesity [2]
ER-alfa / ER-beta
- In adipose tissue associated with
- Obesity
- Serum level and production of leptin in omental adipose tissue [2]
- Localized in:
- Nucleus
- Plasma membrane
- Mitochondria [2]
Estrogen receptor beta signalizace
- ER-beta mediated effects on adipose tissue are opposite of ER-alfa [2]
- ER-beta inhibited ligand-mediated transcriptional activity induced PPAR-gamma [2]
- Blockade of PPAR-gamma-induced adipocytic gene expression
- Decreased adipogenesis
- Involved in the anorectic action of estrogen [2]
- ER-beta is present in mitochondria of
- Uterus
- Ovary
- Rat primary neurons
- Primary cardiomyocytes
- Murine hippocampus cell lines
- The perikarya and proximal dendrites of pyramidal
- Granule cells of rat coronal hippocampus
- Human breast cancer MCF-7
- Liver cancer HepG2 cells
- Heart cells[
- Lens epithelial cells
- Osteosarcoma SaOS-2
- Sperm [1]
- Reduction of ER beta expression by siRNA targeting
- Increased
- Ppar gamma transcript levels
- Stromal fibroblast differentiation into mature adipocytes
- Reversed by GEN but not by DPN [70]
- Transcript levels for Er beta (Esr2)
- Inhibit PPAR gamma activity
- Were downregulated upon MSF differentiation to mature adipocytes [70]
- ER beta
- Exert anti-proliferative (Vivar et al. 2010) and anti-adipogenic (Foryst-Ludwig et al. 2008) effects [70]
Estrogen receptor beta knock out (beta-ERKO) mice
- Insulin resistance
- Impaired glucose tolerance (Heine et al 2000) [1]
- no difference in brown adipose tissue (BAT) weight mice of all ages
- WAT increased with advancing age in male mice (Heine et al 2000) [1]
- Reduced energy expenditure rather than increased energy intake (Heine et al 2000) [1]
- Some mutations in human ER-beta gene
- Obese adolescents and women with bulimic disease [2]
- Inhibitory effects of E2 on food intake and bodyweight blocked
- By anti-sense oligonucleotides of ER-beta in brain
- Not blocked by antisense of ER-alfa [2]
Estrogeny u žen
- estrogen in lipid metabolism in the adipose tissue
- Fat mass is increased in male mice with:
- Homozygous inactivation of ER
- Inaktivace estrogen receptor gene
- Inaktivace aromatase gene [52]
- Stimulate glucose transport and glycolysis in various target organs
- Stimulate FA ß-oxidation
- Several key enzymes in TCA Cycle
- mitochondrial ANT [1]
- E2 and ERs enhance the cellular energy generation and expenditure by stimulating
- MRC function/Oxidative phosphorylation
- ANT shuttling [1]
- Estrogens
- Endogenous estrogens
- 17-beta-estradiol (E2) [2]
- Environmental estrogenic EDCs
- Estrogens regulated the body weight and energy metabolism in the brain
- Similar to that of the leptin
- Involved in the regulation of body weight and obesity
Exenatide
- Glucagon-like peptide [GLP]
- Acting as an incretin hormone [96]
Extracellular signal-regulated kinase (ERK)
- Aktivace vede k lipolýze
Fatty acid beta-oxidation
Fenfluramine
- Withdrawn from the market
- Phentermine with fluoxetine (Prozac) - phen/pro
- Not an accepted treatment for obesity
FGF - Fibroblast growth factor 21 (FGF21)
- 181 amino acid circulating protein
- Member of the FGF superfamily
- Interaction with
- Specific FGF receptors
- Cofactor ß-Klotho
- Expression is predominantly detected in metabolically active organs [47]
Funkce FGF21
- Stimulates glucose uptake in adipocytes
- Via the induction of glucose transporter-1
- Action is additive and independent of insulin
- Preserv beta-Cell function and survival
- Glucagon secretion is reduced by this protein
- Thus decreasing hepatic glucose production
- Improving insulin sensitivity [47]
- Improved Lipid profile in several animal models
- Increases energy expenditure in rodents
- Induces weight loss in diabetic nonhuman primates
- Exerts favorable effects on hepatic steatosis
- Reduces tissue lipid content in rodents
- Adaptive metabolic responses to fasting, including seem to be partially mediated by FGF21
- Stimulation of ketogenesis
- Fatty acid oxidation [47]
Human serum FGF21 concentrations
- Have been found elevated in insulin-resistant states
- Such as impaired glucose tolerance
- Type 2 diabetes [47]
- FGF21 levels correlated with
- Hepatic insulin resistance index
- Fasting blood glucose
- HbA1c
- Blood glucose after an oral glucose tolerance test [47]
- A relationship has been reported between FGF21 levels and
- Long-term diabetic complications
- Nephropathy
- Carotid atheromatosis [47]
- FGF21 levels
- Decreased
- In diabetic patients after starting therapy with insulin or oral agents [47]
- Increased
- Associated with obesity
- In patients with ischemic heart disease [47]
- In children, it is correlated with
- BMI
- Leptin levels [47]
- Circulating FGF21 levels seem to be related to
- Insulin resistance
- Inflammation in dialysis patients [47]
- Hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties [47]
- FGF21
- Affect brown adipocyte activation
- + recruitment of BAT
- Promising for the development of new anti-obesity drugs [77]
Fluoxetine
Follicle-stimulating hormone receptor
- Adult knock out mice gain bodyweight [1]
Forskolin
- CAMP elevating agents
- In brown adipocytes forskolin caused
- 3-fold increase in Erk1/2 phosphorylation
- Similar to the effect of beta-receptor stimulation [76]
- More potent than selective beta-receptor stimulation (i.e.isoprenaline)
- May be due to
- Higher levels of intracellular cAMP generated
- Longer duration of the signal [76]
Fosforylace HSL
- Aktivace HSL
Fungreek fiber
- A significant decrease in appetite [96]
- Mathern et al 2009, Healthy obese [n?=?18), Single blind]
- 4 or 8 gr/3.5 hr
- I: extract
- C: control
- Increased mean ratings of satiety and fullness,
- Reduced ratings of hunger and prospective food consumption
- Reduce energy intake
- No difference for AUC blood glucose, increase in AUC for insulin levels [96]
Phytoestrogens
- Genistein
- Daidzein
- Prevented diabetes onset
- Elevating insulin level
- Reducing hepatic gluconeogese
- Red. hepatic FA beta-oxidation activity in non-obese diabetic (NOD) mice [1]
Fucus - Chaluha bublinatá, pilovitá,
- úlomky sušené stélky
- jod a další látky s vlivem na metabolismus
- U DM2
- Čaj Dolní lipová
- Připravují - zle, vaří - slzy, pijí - umírají
- 2 a více litrů v lázních Dolní Lipová na hubnutí
- Klidné tiché vody Morgehenského zálivu - silné porosty
- Fukoidan, kyselina alginová - bobtnání
- Florothaniny - u DM
- Tetraterpenové pigmenty - beta-karoten
- Vit K,
- Mannitol,
- jod 0,003-0,2 % v org. sloučeninách - vstřebává se
- Důležitý i při DM
- Před užíváním znát stav štítné žlázy
- Nadbytek jodu škodlivý
- Neužívat s jinými jodovými přípravky
Trávicí systém I: Léčiva přírodního původu používaná při obezitě, diabetes mellitus, dislipidemii a nechutenství
prof. Lubomír Opletal: Katedra farmakognozie a farmaceutické botaniky
Plantaginis ovatae / isfagula semeno a osemení jitrocele vejčitého
- Slizy až 30%
- Steroly,
- Iridoidní glykosidy
- Jako objemové laxans - nabobtná - projde střevem
- Doplněk stravy u obezity a hypercholesterolemie
- Celé semeno - množství slizu - sorbuje tuky i cholesterol
- U potíží spolykáním
- 30 ml vody/1g
- Pokud málo tekutin - riziko ucpání jícnu/hrdla
- Alfa amyláza je bloknuta
- KI: striktury v GIT, střevní neprůchodnost - riziko neprůchodnosti
- Nediagnostikované anální krvácení - hemeoridy, nádory (neřekl proč )
- Několik hodin před stolicí - zjemnění
- Večer - ráno
Trávicí systém I: Léčiva přírodního původu používaná při obezitě, diabetes mellitus, dislipidemii a nechutenství
prof. Lubomír Opletal: Katedra farmakognozie a farmaceutické botaniky
Fyzická aktivita
- Ectopic lipid accumulation in skeletal muscle and liver
- Closely associated with insulin resistance syndrome and diabetes [7]
- Flux of muscular fatty acids [7]
- Pivotal role in the development of the abnormalities of muscle and whole-body energy metabolism
- Increase in the consumption of intramuscular lipids via mitochondrial ß-oxidation would be beneficial [7]
- Fyzicka aktivita - ET
- Facilitates hormone-stimulated lipolysis in white adipocytes in mammals
- Adipose triglyceride lipase (ATGL) [7]
- PAT family proteins [7]
- Comparative gene identification-58 (CGI-58) [7]
- Lipotransin [7]
- Fyzickou aktivitou upregulace:
Garcinia Atroviridis
Garcinia cambogia Desr.
- Seeds Extraction by maceration using ethanol as solvent
- Hydroxycitric acid
- Inhibition of the enzyme adenosine triphosphatasecitrato lyase blocking lipogenesis In vivo
- Decrease in plasma level of low density lipoprotein cholesterol
- Increase in the level of chylomicrons In vivo [98]
Genistein
- Dietary exposure to soy foods is associated with
- Lower mammary tumor risk
- Reduced body weight and adiposity in humans and in rodent [70]
- Soy protein isolate and its bioactive isoflavone genistein (GEN)
- Lowered
- Mammary adiposity
- Increased
- Mammary tumor suppressor PTEN
- E-cadherin expression in female mice [70]
- Relative to control casein diet
- GEN showed reductions in
- Mature adipocyte numbers
- Triglyceride accumulation
- Ppar gamma (Pparg) transcript levels
- Fatty acid synthase transcript levels
- GEN inhibition of adipose differentiation was accompanied by
- Increased estrogen receptor beta 2 gene expression
- Modestly recapitulated by ERbeta-selective agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile (DPN) [70]
- Reduction of ER beta expression by siRNA targeting
- Increased
- Ppar gamma transcript levels
- Stromal fibroblast differentiation into mature adipocytes
- Reversed by GEN but not by DPN [70]
- Medium from GEN-treated adipocytes
- Diminished anchorage-independent mammosphere formation of human MCF-7 breast cancer cells
- Direct regulation of mammary adiposity by GEN for breast cancer prevention [70]
- Tumor suppressor induction and oncogene downregulation
- Strong antioxidant activity through redox signaling
- Anti-inflammatory actions through inhibition of pro-inflammatory cytokine expression
- Increased insulin sensitivity
- Anti-adipogenic capacity [70]
- GEN has been shown to decrease body and fat pad weights in rodent models and in humans
- Inhibit adipogenesis and lipid metabolism
- Decreased expression of key lipogenic enzyme genes
- Fatty acid synthase
- Malic enzyme 1 [70]
- GEN inhibition of mammary adipogenesis
- Associated with
- Induction of Er beta (Esr2) expression
- Inhibition of Ppar gamma
- Inhibition of Fasn expression [70]
- ER beta is not the sole mediator of GEN's inhibition of mammary adipocyte differentiation
Glukagon
- Aktivace HSL
Green tea polyphenols - GTP
- Animals fed a high-fat diet for 8 months
- Supplementation of green tea polyphenols (GTP) in drinking water for 4 months in the obese rats
- Decreased body weight (BW)
- -percentage of FM
- + percentage of FFM
- + bone mineral density and strength
- + glutathione peroxidase (GPX) protein expression
- Suppressed serum IGF-I
- -leptin
- -proinflammatory cytokines in the obese rats [20]
- GTP supplementation
- Benefited body composition and bone properties in obese rats
- Enhancing obesity-related anorectic genes
- +anti-oxidative stress capacity
- Suppressing obesity-related orexigenic genes
- Modulating estrogen-associated action [20]
Green tea
- Catechins
- Epigallocatechin gallate (EGCG) reduce:
- Adipocyte differentiation and proliferation
- Lipogenesis
- Body weight
- fat absorption
- Plasma levels of TAG
- Free fatty acids
- cholesterol
- Glucose
- Insulin
- Leptin [1]
- Increase:
- Beta-oxidation
- Thermogenesis [1]
- Targets:
- Adipose tissue
- Liver
- Intestine
- Skeletal muscle
- In high-fat-fed mice EGCG inhibited
- Obesity
- Metabolic syndrome
- Fatty liver disease [1]
- Seem to have satisfactory anti-obesity effects [96]
- Green tea consumption in human studies
- Not all studies have found positive results for obesity-related measures
- 12-week green tea supplementation to a low-energy diet
- Independent of habitual caffeine intake
- no effect on measures of BW or body composition in overweight women at 4 weeks or 3 months [20]
- Randomized, double-blinded, placebo-controlled trial in Taiwan, Hsu et al.
- no statistical difference in % reduction in BW, BMI, and waist circumference between
- Placebo x the GTE-supplemented (491 mg catechins) after 12 weeks [20]
Hořčík, zinek, chrom
- Snižují chuť na sladké
Hormone sensitive lipase
Hormony štítné žlázy
- Maintenance of energy balance
- Regulating the differentiation process in many tissues including the adipose tissue
- Transcription factors (c/EBPs, PPARs)
- Activate specific genes, resulting in the adipocyte phenotype [80]
- Aktivace HSL
T3 modulated
- Corepressors
- Coactivators
- Thyroid hormone concentrations
- In tissues
- By the action of the deiodinases D1, D2, and D3
- Control the amount required in each tissue [80]
- Adipogenesis
- Lipogenesis
- Lipolysis in vivo as well as in cultures of adipocytes (Oppenheimer et al., 1991; Ailhaud et al., 1992) [80]
- Genes expressed during the differentiation
- May bind the TREs present in the gene promoters
- GPD, ME, PEPCK, S14 (Kinlaw et al., 1995)
- FAS (Moustaid and Sul, 1991)
- GLUT4, and LPL (Mariash et al., 1980; Blennemann et al., 1995; Bianco et al., 1998) [80]
- PPARs
- Retinoic acid receptors (Silva and Rabelo, 1997)
- Insulin (IRE)
- CAMP response elements (CREs)
- Cross-talk among the regulatory elements
- TREs, RAREs, PPARs of the nuclear receptors
- Many of them share RXR as pattern of dimerizacion
- Coactivators
- UCP-1, ME, ACC and others (Mullur et al., 2014)
- At the transcriptional level
- Stabilizes the mRNAs produced
- ATGL/desnutrin/Pnpla2 (Ahmadian et al., 2010, 2011)
- Several genes involved in
- Lipid mobilization
- Storage
- Thermogenesis
- WAT and BAT are targets of thyroid hormones [80]
- Gluconeogenesis and glycolysis
T3 synergize / increase
- Insulin (Hernandez et al., 1993) [80]
- Stimulate adiponutrin (Adpn, Pnpla3, also called acylglycerol-O-acyltransferase or calcium-independent phospholipase A2 epsilon, iPLA2-epsilon)
- Triacylglycerol lipase
- Strongly upregulated by T3 in rat and human white and brown adipocytes (Calvo and Obregon, 2009) [80]
- Lipase with double action
- Lipase involved the hydrolysis of triacylglycerol
- In acyl-CoA transacylation of acyl-glycerols
- Involved in lipid homeostasis [80]
- Fatty acids oxidation in BAT (Christoffolete et al., 2004; Castillo et al., 2011)
- T3 accelerate fatty acid oxidation and lipogenesis in BAT
- Lack of T3 in D2KO mice
- Impairs thermogenesis
- Mice survive thanks to compensatory mechanisms in the sympathetic system and increased lipolysis
- Important for Glut4 expression up regulated by T3 in brown adipocytes
- Glut4 promoter TRE
- Glut4 carbohydrate responsive element binding protein (Chrebp)
- Increases ion transport
- Increasing several transporters (SLCs)
- Tramdorin in the plasma membrane
- mitochondrial transporters
- Increasing structural genes
- Keratins (Martinez-De-Mena and Obregon, 2014)
- Increasing enzymes involved in
- Degradation of metabolites
- Decreasing TSH receptors
- In cultured brown adipocytes
- T3 is required for
- UCP-1 adrenergic increases
- Stabilization of mRNA transcripts (Hernandez and Obregon, 2000)
T3 Snižuje
- LPL down regulated by T3
- Upregulated when T3+NE is added (Medina-Gomez et al., 2003, 2008) [80]
- Seem to be anti-mitogenic
- T3 inhibits bFGF and aFGF mitogenic effect in brown preadipocytes (Garcia and Obregon, 2002) [80]
Deiodinases D3, D2, and D1
- Regulate the availability of T3
- D3 is activated during proliferation
- D2 is linked to the adipocyte differentiation program
- Providing T3 needed for lipogenesis and thermogenesis
- Supply of thyroid hormones is finely tuned and regulated in a time- and dose-specific way in specific areas of the brain
- Sequential increases or decreases in D2 and D3 deiodinases [80]
D3 - type III deiodinase
- Activity and mRNA
- Strongly induced by growth factors in brown adipocytes (Hernandez and Obregon, 1995; Hernandez et al., 1998)
- As in other proliferating cells
- Importance of low T3 levels during proliferation
- Increases abruptly when serum is added to cultures of brown adipocytes (Hernandez et al., 2007)
- Mitogenic marker in brown preadipocytes
Conversion of T4 to T3
- Required for
- Thermogenic function of BAT (Bianco and Silva, 1987)
- Stimulation of D2 (Hernandez and Obregon, 1996b; Martinez-Demena et al., 2002)
- D2 participates in the formation of BAT (Carmona et al., 2002)
- With low UCP1 mRNA, D2 activity, and low mitochondriogenesis
- Implicated in the process of lipogenesis under adrenergic stimuli (Bianco et al., 1998)
T3 modulated
- Corepressors
- Coactivators
- Thyroid hormone concentrations
- In tissues
- By the action of the deiodinases D1, D2, and D3
- Control the amount required in each tissue [80]
- T3 regulates
- Adipogenesis
- Lipogenesis
- Lipolysis in vivo as well as in cultures of adipocytes (Oppenheimer et al., 1991; Ailhaud et al., 1992) [80]
- Regulate genes expressed during the differentiation
- May bind the TREs present in the gene promoters
- GPD, ME, PEPCK, S14 (Kinlaw et al., 1995)
- FAS (Moustaid and Sul, 1991)
- GLUT4, and LPL (Mariash et al., 1980; Blennemann et al., 1995; Bianco et al., 1998) [80]
- PPARs
- Retinoic acid receptors (Silva and Rabelo, 1997)
- Insulin (IRE)
- CAMP response elements (CREs)
- Cross-talk among the regulatory elements
- TREs, RAREs, PPARs of the nuclear receptors
- Many of them share RXR as pattern of dimerizacion
- Coactivators
- UCP-1, ME, ACC and others (Mullur et al., 2014)
- Acts at the transcriptional level
- Stabilizes the mRNAs produced
- T3 effects synergize with insulin (Hernandez et al., 1993) [80]
- T3 stimulate adiponutrin (Adpn, Pnpla3, also called acylglycerol-O-acyltransferase or calcium-independent phospholipase A2 epsilon, iPLA2-epsilon)
- Triacylglycerol lipase
- Strongly upregulated by T3 in rat and human white and brown adipocytes (Calvo and Obregon, 2009) [80]
- Lipase with double action
- Lipase involved the hydrolysis of triacylglycerol
- In acyl-CoA transacylation of acyl-glycerols
- Involved in lipid homeostasis [80]
- ATGL/desnutrin/Pnpla2 (Ahmadian et al., 2010, 2011)
- LPL
- Down regulated by T3
- Upregulated when T3+NE is added (Medina-Gomez et al., 2003, 2008) [80]
Deiodinases D3, D2, and D1
- Regulate the availability of T3
- D3 is activated during proliferation
- D2 is linked to the adipocyte differentiation program
- Providing T3 needed for lipogenesis and thermogenesis
- Supply of thyroid hormones is finely tuned and regulated in a time- and dose-specific way in specific areas of the brain
- Sequential increases or decreases in D2 and D3 deiodinases [80]
D3 - type III deiodinase
- Activity and mRNA
- Strongly induced by growth factors in brown adipocytes (Hernandez and Obregon, 1995; Hernandez et al., 1998)
- As in other proliferating cells
- Importance of low T3 levels during proliferation
- Increases abruptly when serum is added to cultures of brown adipocytes (Hernandez et al., 2007)
- Mitogenic marker in brown preadipocytes
D2
- Activity
- Low during proliferation
- Opposite role in BAT než D3
T3 regulates several genes involved in
- Lipid mobilization
- Storage
- Thermogenesis
- WAT and BAT are targets of thyroid hormones [80]
TRs
- T3 acts through their nuclear receptors
- Specific TRs in the gene promoters
- Regulating transcription factors
- Encoded by two genes TR alpha and TR beta
- Different isoforms: TR alpha-1, TR alpha-2, and TR beta-1 [80]
- Bind to thyroid response elements (TREs)
- Present in the promoters of the target genes
- Forming heterodimers with RXR [80]
- Isoforms of thyroid hormone receptors present in WAT and BAT
- TR alpha-1
- More abundant (Bianco and Silva, 1988; Teboul and Torresani, 1993; Tuca et al., 1993; Hernandez and Obregon, 1996a)
- TR alpha-2
- TR beta-1 [80]
HSL
- Located entirely in the cytoplasm
- Nonphosphorylated and removed from lipid droplets
- Reducing the hydrolysis activity of TG in adipocytes
- HSL is a substrate of activated ERK
- Site-directed mutagenesis of putative ERK consensus phosphorylation sites in HSL identified
- HSL Ser(600)
- Phosphorylated by active ERK
- Mutace S600A HSL expressed in 3T3-L1 cells expressing the regulatable Raf
- Tamoxifen treatment fails to increase its activity [13]
- Activation of the ERK pathway
- Able to regulate adipocyte lipolysis
- By phosphorylating HSL on Ser(600)
- Increasing the activity of HSL [13]
- Hormonally stimulated lipolysis
- By activation of cyclic AMP-dependent protein kinase (PKA)
- Phosphorylates hormone-sensitive lipase (HSL)
- Increases adipocyte lipolysis [77]
- Catecholamines activate
- PKA
- Mitogen-activated protein kinase pathway
- Extracellular signal-regulated kinase (ERK) [77]
Hormonal activation of beta-ARs-PKA
- Provokes the association of CGI-58 with ATGL in fragmented lipid droplets
- Within minutes, dissociation of PKA-phosphorylated perilipin 1 at Ser517 and CGI-58
- PKA promotes
- Phosphorylation HSL at Ser659 and Ser660
- Translocation of phosphorylated HSL from the cytoplasm to lipid droplets
- Perilipin 1 acts as a scaffold protein to bind HSL with lipid droplets
- Results in an inducement of the maximal lipolytic response
- Support the localization of lipases
- Critical role in the adaptive alteration of the lipolytic response in white adipocytes by physical exercise
Hunteria umbellata (K. Schum) Hallier f.
- Ghana Gabon [99]
- Inhibition of intestinal absorption and lipid biosynthesis In vivo
- Seeds Extraction by maceration using water as solvent
- Alkaloids [98]
Hypoxia
- Can occur in AT when
- Adipocytes expand in excess of microvasculature growth
- When adipocyte size exceeds the diffusion of nutrients [38]
Ilex paraguariensis A. St.-Hil.
- Protective effect against obesity induced in rats through
- Increased expression of decoupling proteins
- Raised ampk phosphorylation in visceral adipose tissue
- Leaf Decoction extraction using water as the solvent
- Alkaloids (cafeinne)
- Saponins [98]
- In vivo
- Leaf Extraction by maceration using water as solvent
- Methylxanthines (theophylline),
- Saponins,
- Alkaloids (caffeine and theobromine) [98]
2-Hydroxy-N-arylbenzenesulfonamide 9
- Modest inhibitor of ACL with 50% inhibition of ACL activity (IC50 ) at 1.1 M)
- Long-term oral dosing of compound 9 in high-fat-fed mice lowered down plasma cholesterol, triglyceride, and glucose and blocked weight gain.
- 2-hydroxy-N-arylbenzenesulfo-namide 9 is the most potent ACL inhibitor with appreciable cell permeability.
Insulin-like growth factor-1 - IGF-I
- Attenuated tumor necrosis factor-alpha induced apoptosis in cultured fetal brown adipocytes [63]
- Seems to be an important mitogen for fetal brown adipocytes
Irisine
- Affect brown adipocyte activation
- + recruitment of BAT
- Promising for the development of new anti-obesity drugs [77]
Irvingia Gabonensis
- West african plants
- Show significant decreases in body weight in studies
- Significant decrease in body fat [96]
- Significant decrease in waist and hip circumferences [96]
- Ngondi et al 2009 [22] Over wt. &/or obese [n?=?102]
- 150 mg /10 wk
- Sig. improvements in BW, body fat, and WC
- Sig. improvements in plasma TC, LDL-chol, BS, CRP, adiponectin and leptin levels 97.9?±?9.1 85.1?±?3.1 <0.01 [96]
Isoprenaline
- Promoted the survival of the BAT
Katecholaminy
- Aktivace HSL
Krebsův cyklus
K. arachodinovoá
- Fatty acid arachidonic
- Good mitogen for brown adipocytes [80]
Lagerstroemia speciosa (L.) Pers.
- Leaf Extraction by maceration using water and methanol as solvents
- Tannins [98]
Leptin
- Secreted from adipose cells
- Attenuates food intake
- Increases energy expenditure (Halaas et al., 1995) [1]
- Decreases appetite [1]
- Plasma maximum level midway through a normal nocturnal sleep period (Simon et al., 1998) [1]
- Lower levels of plasma leptin related to sleep loss thus
- Contribute to increased appetite [1]
- Leptin anorexigenic function
- Via neuropeptide alpha MSH
- Produced by ARC neurons
- Binds to the melanocortin receptors
- Pathway is disrupted in Ay/a and Mc4-r-deficient mice
- Do not display any bone mass abnormality
Administration of leptin
- In the neonatal period - or via the mother hlodavcům
- Prevents the development of the metabolic phenotype and adiposity (Stocker et al 2004; Vickers et al 2005) [1]
- Reversal of the changes in gene expression and methylation in liver tissue when examined as adults (Gluckman et al 2007c) [1]
- May be acting by effects on neonatal food intake
- Effects on hypothalamic maturation (Bouret et al 2004) [1]
- Critical period ?? [1]
- Leptin
- Induce a reduction in fat pads weight
- After peripheral or central injection
- Intracerebroventricular administration of leptin in rats
- Adipocyte apoptosis [78]
- Induces an increased SNS activity [78]
- Signal that promotes apoptosis under leptin CNS activation is probably NE or another co-secreted neurotransmitter [78]
Blokáda panktreatické lipázy
- Decreased energy intake from the GIT
- Distinct types of tea
- Green
- Oolong
- Black tea [96]
- Strong inhibitory activity against pancreatic lipase, which led to weight loss
- L-epicatechin
- Epicatechin-3-gallate
- Epigallocatechin
- Epigallocatechin-3-gallate [96]
Lipolýza v tukové tkáni - Lipolytic cascade
Beta 1-, beta 2-, and beta 3-adrenergic receptors (ß-ARs)
- Stimulation of G-protein coupled receptors (GPCRs)
- GDP release
- GTP binding
- Activation of adenylyl cyclase (AC)
- Production of cAMP + (=aktivace lipolýzy)
- Increased intracellular cAMP level
- Phosphorylates and activates cAMP-dependent protein kinase A (PKA)
- Phosphorylates hormone-sensitive lipase (HSL) [7]
- CAMP-dependent protein kinase (PKA) phosphorylation of HSL at:
- Ser563
- Ser659
- Ser660 [7]
- Enhances its enzymatic activity
- Extracellular-regulated kinase (ERK)
- Induces the phosphorylation of HSL at Ser600 in 3T3-L1 adipocytes [7]
- Phosphorylated HSL
- Activates the hydrolysis of TG in adipocytes
- Translocation of HSL from the cytoplasm to the surface of lipid droplets
Alpha 2-adrenergic receptor, adenosine receptor, prostaglandin E2 receptor
- Stimulate Galpha i
- Inactivation of AC
- Reduces the production of cAMP (=stop lipolýzy)
- Attenuation of the lipolytic response [7]
Adipose triglyceride lipase (ATGL)
- no specificity for the hydrolysis of MG, cholesterol esters, or retinyl esters
- TG that is 10-fold higher than that for DG
- Hydrolytic function is not restricted to the catabolism of lipid droplets in adipose tissue
- ATGL initiates lipolysis by removing the first FA from TG to, in turn, produce DG
- HSL generates an additional FA from DG and MG to produce glycerol
- Phosphorylation of lipases plays a central role in the regulation of enzyme activity
- ATGL protein are significantly increased in human skeletal muscle by fyzicka aktivita
Insulin
- Increases in phosphodiesterase-3B (PDE-3B) activity
- Snižuje intracellular cAMP [7]
- Changes cAMP to AMP via the activation of protein kinase B/AKT [7]
- Inhibitory effect of insulin
- On HSL activity
- Increase in its phosphorylation at Ser565
- AMP activated protein kinase (AMPK)
alfa--AR-cAMP production
- ?2-ARs modulate lipolysis at rest [7]
- Complete activation of lipolysis in white adipocytes [7]
- Only when catecholamines were in the presence of an ?2-AR antagonist in human [7]
- ?2-antilipolytic component counteracting the ß-AR-mediated lipolysis [7]
- Well known as the “?2/ß-adrenergic balance”
beta-AR-cAMP production
- ß-ARs modulate lipolysis during physical exercise [7]
- Even if ?2/ß-adrenergic balance exists in human white adipocytes [7]
- Number of ?2-ARs in jerboa, dormouse, and rat is lower than that in humans [7]
Lipotransin
- Facilitates hormone-stimulated lipolysis in white adipocytes in mammals [7]
Lorcaserin hydrochloride (Belviq)
- Novel selective serotonin 2C (5-HT2C) receptor agonist
- Modulates food intake in hypothalamus [96]
- June 2012
- Controlling appetite (via serotonin activation)
- Nearly half the patients using the medication lost at least 5% of their starting weight
- More than double in the control group
- Only true for patients without type 2 diabetes.
- Approved for patients who are
- Obese (BMI >30)
- Overweight (BMQ >27) with one weight-related health issue
- Predominant side effects
- Headache
- Dizziness
- Fatigue
LPL
- Down regulated by T3
- Upregulated when T3+NE is added (Medina-Gomez et al., 2003, 2008) [80]
Lycium barbarum
- Significant decrease in waist and hip circumferences [96]
- Amagase et al 2011, Healthy over wt. Lycium barbarum
- 30, 60, and 120 ml/14 d
- I: extract
- C: control
- Increase of postprandial energy expenditure
- Sig. decrease in WC
- Increase in metabolic rate [96]
ATMs (adipous tissue macrophages)
- Recruited to phagocytose cellular debris following adipocyte apoptosis
- Can be visualized in the CLS in obese AT
- Clearance of dead adipocytes is driven by inflammatory cytokines
- Presence of classically activated macrophages may contribute to collagen deposition and AT fibrosis in mice [38]
- ATM apoptosis being important for maintenance of AT homeostasis
- Clodronate liposome-mediated depletion of ATMs from obese mice
- Reduces AT inflammation
- Improves insulin sensitivity [38]
- Loss of M1 inflammatory macrophages can improve AT function
- Treatment of humans with the insulin sensitizing drug pioglitazone
- Reduces the number of macrophages in AT via apoptotic mechanisms [38]
Databáze potravin metabolic balance®
- Revised German Nutrient Data Base (BLS)
- Lists every available food along with all of its nutrient ingredients
Kulturisté v metabolic balance®
- Special nutritional plans for body builders
- Following criteria "20-30-40"
- Body fat percentage less than 20 %
- BMI greater than 30
- Biceps circumference greater than 40 cm
Děti v metabolic balance®
- After the 8th year of life
- Advised during the holiday period
- Makes sense for children to avoid eating wheat and milk products
- Adjusting their diet particularly toward foods with a low glycemic load
MEK aktivace
Metformin
- Asociován s poklesem hmotnosti
Metylace - Různost genové exprese
- During prenatal and early postnatal development and function throughout life
- Diverse gene expression
Methylation of cytosines
- Within CpG dinucleotides
Modifications of the histone proteins
- Package DNA in the nucleus
Cell-autonomous expression of myriad autoregulatory DNA binding proteins
Methyl supplementation
Myši
- Female mice before and during pregnancy
- Induces DNA hypermethylation at “metastable epialleles” in the offspring, with permanent phenotypic consequences:
- Agouti viable yellow (Avy) (Waterland and Jirtle, 2003)[1]
- Axin fused (Waterland et al., 2006) [1]
Prevence epigenetického imprintingu
Myši
- Obézní matkou dávaná epigentická dispozice k obezitě
- Lze vyrušit methyl donor supplementation
- Role of DNA methylation in transgenerational amplification of obesity ? (Waterland et al, 2008)[1]
Mononenasycené kyseliny
- Mandle
- Vlašské ořechy
- Semena
- Olivový olej
- Olivy
- Avokádo
- Lískové oříšky
- Makadamové a kešu ořechy
- Obzvláště u jedinců s výhodným polymorfismem genu ADIPOQ
- Přispívají k mírnému poklesu BMI (LifeTest)
- Snižují LDL cholesterol a zvyšují HDL
Monoselect Camellia
- Show significant decreases in body weight in studies
- Significant decrease in body weight [96]
- Reduced the waistline only in men [96]
Moringa oleifera Lam.
- Reduction of atherogenic index
- Reversing the hyperlipidemic effect produced by high fat diet In vivo
- Leaf Extraction by maceration using methanol as solvent
- Fitotesrol
- ß-sitosterol [98]
Morus bombycis Koidz.
- Increased lipolytic effects
- Decreased intracellular triglycerides
- Release of glycerol In vitro
- Leaf Reflux extraction using ethanol at 70° as solvent
- Alkaloids [98]
Nelumbo nucifera Gaertn.
- Inhibition dependent on the concentration of ?-amylase and lipase activity
- Over-regulated lipid metabolism and the expression regulation of gene expression in skeletal muscle In vivo/in vitro
- Leaf Reflux extraction using 15% aqueous ethanol as solvent
- Alkaloids [98]
Nigella Sativa
- Show significant decreases in body weight in studies
- Seem to have satisfactory anti-obesity effects
- Effect size of these medicinal plants is a critical point that should be considered for interpretation [96]
- no report for side effect in these trials
- Safety of these plants still remains to be elucidated by further long-term studies [96]
- Significant decrease in body weight [96]
- Significant decrease in waist and hip circumferences [96]
Norepinephrine (NE)
- Increase in the amount of UCP
- Stimulating its gene transcription [78]
- Inhibits proliferation of adipocyte precursor cells in vitro
- Can be blocked by propranolol - general ß-adrenoceptor antagonist [78]
- Stimulated
- Phosphorylation and the activity of Erk1/2 via the Erk kinase MEK
- Expression and secretion of basic fibroblast growth factor (bFGF)
- Further promoted the cell survival via MEK-dependent activation of Erk1/2
- Protected the cells form apoptosis
- Agonist stimulation of alpha 1- and beta-adrenergic receptors
- Increases intracellular level of Ca2+ and cAMP stimulated the phosphorylation of Erk1/2
- Promoted the cell survival
- Hyperplasia and in the differentiation of BAT
- NE also stimulated the expression and secretion of bFGF from the cells
- Further promoted the cell survival via MEK-dependent activation of Erk1/2 [76]
- Effect of NE treatment on the cell survival remained for at least 2 days
- Despite removal of the hormone [76]
- Brown adipocytes
- Pro-apoptotic effect of TNFa [78]
- Abrogated by Norepinefrin
- Protects the cells from apoptosis [78]
- CAMP level in brown adipocytes remains markedly elevated after 30 min of NE stimulation
- NE also activates inhibitory signals
- protein phosphatase(s)
- Could limit the activation of Erk [76]
- norepinephrine infusion at 25 degrees C
- Mimicked the effects of cold exposure on the coordinated proliferation of the different cellular types
- Intact sympathetic nerves
- Required for the stimulation of mitotic activity in BAT by cold exposure
- But not by norepinephrine infusion
- norepinephrine release from sympathetic nerves
- Represents the initial stimulus in a chain of metabolic events leading to BAT hyperplasia
- Sympathetic or sensory nerves
- May still contain factors modulating cell proliferation and differentiation in BAT
- Poor mitogen itself
- Increases
- The mitogenic action of serum
- Growth factors
- Vasopressin [80]
- Producing true brown adipocytes that express UCP1
- Increasing UCP1 expression [80]
Norepinephrine
- Increase in the amount of UCP
- Stimulating its gene transcription [78]
- Inhibits proliferation of adipocyte precursor cells in vitro
- Can be blocked by propranolol - general ß-adrenoceptor antagonist [78]
- Brown adipocytes
- Pro-apoptotic effect of TNFa [78]
- Abrogated by Norepinefrin
- Protects the cells from apoptosis [78]
Virgin olive oil
- Significant decrease in body weight [96]
Omega 3 Mk
- 1997 okuno publikoval že omega-3 mastné kyseliny (alfa-linolenová kyselina) vedla k hypoplazii a hypotrofii tukové tkáně
- Na rozdlíl od podávání stravy obohacené o mononesaturované (kyselina olejová) nebo polynesaturované mastné kyseliny omega-6 MK (k. linolová)
BalanceOil
Omega 3 Mk
- Omega-3 PUFA in modulating this risk of obezity
- Promote the mobilization of triglycerides from adipose sources
- Impact of genetic mutations that promote the abdominal obesity was found to be favourably modulated by plasma omega-3 PUFA
- Adiponectin, leptin and tumor necrosis factor alpha - adipocytokines
- Related to omega-3 PUFA in European whites
- adiponectin
- Associated with plasma levels of omega-3 PUFA
- May be explained by fluctuations of body weight
- Weight loss due to calorie restriction amongst obese subjects
- Results in an alteration in the profiles of serum fatty acids
- Namely greater omega-3 PUFA
- Omega-3 PUFA such as DHA levels
- Low in obese subjects
- Normalized with weight los
- www.sciencedirect.com/science/article/pii/S1538783622115254
Oolong tea
- Show significant decreases in body weight in studies [96]
- Oolong tea showed a decrease in subcutaneous fat content
- Not total body fat [96]
- He et al 2009 [20] Diet induced obese or over wt. [n = 102]
- 8 g/6 wk
- I: extract
- C: control
- Sig. decrease in BW
- Decrease in subcutaneous fat content
- Decrease TC & TG plasma levels 74.1 ± 8.2 71.2 ± 8.1 <0.05 [96]
Orlistat (Xenical, alli)
- Approved by the US food and drug administration for long-term treatment in obese patients [96]
- Adverse gastrointestinal side effects such as steatorrhea [97]
- Lipase inhibitors, or fat blockers
- Orlistat prevents the intestinal absorption of fat by 30%
- Do not affect brain chemistry
- Ali The OTC preparation
- Has a lower dosage than prescription Xenical
- Irregularities in the menstrual cycle
- Interactions
- PAD, thyroid hormons,imunosupressants, warfarine
- Deficiency of fat-soluble vitamins
- A, D, E, K
Otužování - cold exposure
- Acute thermogenic response to low ambient temperature is mediated by NE
- Released from sympathetic neurones innervating the tissue
- Recruitment phase involving mitochondriogenesis
- Increased protein, and DNA synthesis
- Increase in the number of cells in the tissue
- Markedly increased the phosphorylation of mitogen-activated protein kinase (p42/p44) Erk1 and Erk2 in brown adipose tissue
- Protected cells in the tissue from apoptosis
- Cessation of the sympathetic stimulus
- Caused an increased rate of apoptosis in the tissue
- Acute cold exposure (less than 5 h)
- Did not alter the rate of normal cell death (apoptosis) significantly
- Cold exposure (4 °C) within 24 h
- Rate of apoptosis in BAT was markedly reduced
- As long as the animals were exposed to the cold
- Thermoneutral temperature (28°C)
- Decreased sympathetic stimulation of the tissue
- Rate of apoptosis increased within 10 days
- Reaching control level after 20 days [78]
- Cold exposure of the animals
- Rapid increase in the phosphorylation of Erk1/2 in BAT
- Already within 30 min
- Phosphorylation level was sustained as long as the animals were exposed to the cold [76]
- Effects of cold exposure (4 days at 5 degrees C)
- Chronic norepinephrine treatment (0.375 mumol/h for 4 days at 25 degrees C)
- Intact and denervated interscapular BAT pads of adult rats
- Denervated pads
- Paler than the innervated sides
- Contained numerous adipocytes filled with large lipid droplets
- Effects of cold exposure on cell proliferation were markedly inhibited [77]
- Innervated BAT pad
- Cold exposure markedly enhanced the labeling frequency in brown adipocyte precursor cells
- Interstitial cells and preadipocytes
- Endothelial cells forming the numerous blood capillaries [77]
Virgin olive oil
- Show significant decreases in body weight in studies
Stimulace oxidace MK
- Causing a higher fat oxidation in human
- Activating lipid metabolism
- Acceleration of oxidation
- Suppression of fatty acid synthesis
- PPARc agonistic activity [96]
- Epigallocatechin-3-gallate of green tea
- Virgin olive oil
- Capsinoids
- Lycium Brbarum [96]
Oxyntomodulin
- A glucagon-like peptide 1(GLP-1) receptor agonist
- Regulate food intake [96]
Panax japonicus (Nees) C.A. Mey.
- Rhizomes
- Refluxing using methanol as solvent
- Saponins [98]
PAT family proteins [7]
- Facilitates hormone-stimulated lipolysis in white adipocytes in mammals [7]
Perilipin 1
- Member of the perilipin, adipophilin, and TIP47 family
- PAT/perilipin family protein
- Part of lipid droplet-coated proteins
- Expressed mostly in
- White adipose tissue
- Steroidogenic tissue
- Coats lipid droplets
- Six phosphorylation sites in adipocytes by PKA
- Ser81, Ser222, Ser276, Ser433, Ser492, and Ser517
- Multifunctional
- Capable of reducing basal lipolysis
- Via combining HSL with lipid droplets to form a barrier
- Promotes the lipolysis movement of perilipin 1 away from fat droplets
- Through lipase-dependent and -independent mechanisms
Perilipin A
Lipid peroxidation in plasma or liver decrease
- Seem a mechanism of anti-obesity effect [96]
Green tea
- Due to its high concentration of catechins [96]
Persicaria hydropiper L. Leaf
- Extraction using methanol as solvent
- Flavonoids [98]
PGC-1
- Coactivator of PPAR gamma
- Identified in 1998 (Puigserver et al., 1998)
- Cold exposure PGC-1 increases in BAT
- Increases the transcriptional activity of PPAR gamma on the UCP1 promoter
- Overexpression of PGC-1 in white adipocytes
- Results in UCP-1 increases
- Incr. mitochondrial enzymes
- Marker of brown adipocytes and activator of BAT (Puigserver et al., 1998) [80]
- Fundamental for
- Hepatic gluconeogenesis
- Heart function
- Inflammation (Puigserver and Spiegelman, 2003; Handschin and Spiegelman, 2006; Uldry et al., 2006) [80]
- Targeted deletion of PGC1 alpha mice
- Hepatic steatosis
- Increase in body fat
- Lower amount of mitochondria
- Lower respiratory capacity
- Abnormal cardiac function (Leone et al., 2005) [80]
Prostaglandin E2 receptor
- Stimulate Galpha i
- Inactivation of AC
- Reduces the production of cAMP (=stop lipolýzy)
- Attenuation of the lipolytic response [7]
Phenolic compounds
- All are listed as having anti-obesity activity:
- Especially flavones, flavanols, flavanones, catechins, anthocyanins, isoflavones and chalcones
- Their functional derivatives
- Present a variety of chemical structures
- Constituents in fruits, legumes, nuts, beverages and medications
- Predominant in the plant species
- Acacia mearnsii De Wild.
- Achyranthes aspera L.
- Akebia quinata (Houtt.) Decne.
- Artemisia princeps Pamp.
- Persicaria hydropiper L.
- Achyrocline satureioides (Lam.) DC.
- Camellia thea Link.
- Carica papaya L. [97]
Phentermine (Fastin, Adipex P)
- Suppresses appetite
- By release of norepinephrine in the body
- Side effects of phentermine
- Headache
- Insomnia
- Irritability
- Nervousness
Pistachio
- Show significant decreases in body weight in studies
- Li et al 2010, Human [n?=?59] Pistachio
- 53g/12 wk
- Reduced BMI
- Lower TG levels 86.0 6 1.4 82.3 6 1.6 <0.01 [96]
Vylačnění a chuť se hýbat
- Um gesund zu bleiben, braucht der Körper Fastenzeiten zwischen den Mahlzeiten
- Forschungsgruppe von Markus Stoffel, Professor am Institut für Molekulare Systembiologie der ETH Zürich:
Hunger macht aktiv
Transkriptionsfaktor namens Foxa2
- In der Leber
- Fettverbrennung beeinflusst
- Hypothalamus
- Insulin hemmt Foxa2
- Im nüchternen Zustandist Foxa2 aktiv
- Foxa2 Bildung von zwei Eiweissstoffen:
- MCH
- Orexin [1]
- Nahrungsaufnahme und spontane Bewegung
- Haben Säugetiere Hunger, sind sie aufmerksamer, körperlich aktiver.
- Sie jagen, suchen nach Nahrung. [1]
- Bewegungsarmut von fettleibigen Menschen und Tieren
- Foxa2 trvale inaktivní [1]
- Důsledek nebo příčina ? V.s. obojí.
- Genetisch veränderten Mäuse - Foxa2 immer aktiv
- Produzieren mehr MCH und Orexin
- Bewegen sich 5x mehr als gewöhnliche Tiere
- Verlieren Fettgewebe und bilden grössere Muskeln aus
- Zucker- und Fettstoffwechsel Blutwerte sind deutlich besser [1]
Drei Mahlzeiten am Tag genügen
- Der Körper braucht Fastenperioden, um gesund zu bleiben. [1]
- Lieber wenige Male richtig essen, und dazwischen auch dem Hunger Raum zu lassen. [1]
- Denn weil bei jeder Mahlzeit auch Insulin ausgeschüttet wird, das Foxa2 unterdrückt, verringert sich zusehends die Motivation zur körperlichen Aktivität und die Verbrennung von Zucker und Fett. [1]
Literatura:
[1] CLAUDIA NAEGELI. Bewegung kommt mit dem Appetit. URL < idw-online.de/pages/de/news?print=1&id=347276 >.PPAR alpha
- In the liver [80]
Mutations in the TR alpha gene (P398H mutation) induce
- Increased body fat
- Visceral adiposity
- Elevated basal glucose
- Impaired lipolysis
- Hyperleptinemia
- Reduced adaptive thermogenesis (Liu et al., 2003)
- Reduces the binding of PPAR alpha to PPRE elements
- Interfering with PPAR alpha signaling (Liu et al., 2007) [80]
Prdm16
- Expression in white adipocytes of key molecules involved in brown adipocyte differentiation
- Prdm16
- Induce obesity resistance
- Ameliorate insulin sensitivity [77]
Preadipocyte factor 1 - Pref-1 - Dlk1
- Imprinted gene found in preadipocytes
- Potent inhibitor of adipogenesis
- Activates ERK phosphorylation
- Marker of proliferation of brown preadipocytes [80]
Proteinkináza A
- Catecholamines
- Activate PKA
- Mitogen-activated protein kinase pathway (MEK)
- Extracellular signal-regulated kinase (ERK)
- Aktivace lipolýzy
Psyllium fibre
- Show significant decreases in body weight in studies
- Significant decrease in body fat [96]
- Pal et al 2011, Over wt. & Obese Psyllium Fibre
- 12 wk
- I: healthy diet?+?fibre, fibre
- C: placebo
- C: healthy diet?+placebo
- Significant decrease in wt., BMI & %total body fat
- Reduction in TG, insulin,TC & LDL-chol [96]
Pten
- Associated to lean phenotypes
- Overexpression of Pten results in a phenotype with high UCP1
- Pten promoting energy expenditure (Ortega-Molina et al., 2012)
PYY 3–36
RCM-104 compound of Camellia Sinensis
- Compound of
- Camellia Sinensis [Lu Cha Ye—Green tea]
- Semen Cassiae [Jue Ming Zi]
- Flos Sophorae [Huai Hua]
- Show significant decreases in body weight in studies
- Significant decrease in body fat [96]
- Lenon et al 2012 , Obese [n?=?117], double blind
- 500 mg granule extract 4 Cap per time
- 3 times per d
- 12 wk
- Reduced wt., BMI and body fat
- Non-Sig. changes in food intake
- Sig. improvements in quality of life of participants 99.5?±?15.1 98.0?±?15.4 0.002 [96]
Recruitment of precursor cells
- Interscapular and inguinal subcutaneous depots
- Direct conversion of a subpopulation of unilocular/paucilocular adipocytes
- Via beta-AR activation
- Probably driven by beta1-AR
Resveratrol
- Down-regulate the expression of key genes involved in adipocyte differentiation including
- C/EBP?
- PPAR?
- AP2
- Induce G0/G1 and G2/M cell cycle arrest
- Apoptosis of adipocytes
- + of DNA fragmentation
- + caspase-3 activation
- Inactivated NF-kappa B and MAPK
- Inhibits adipocyte differentiation
- Inhib. de novo lipogenesis
- Stimulates lipolysis in adipocyte
- In a Sirt1-dependent manner
- Via activation of AMPK
Sambucus Nigra
Sea buckthorn
- Show significant decreases in body weight in studies
- Significant decrease in waist and hip circumferences [96]
Seaweed laminaria digitata
- Significant decrease in body weight [96]
Sertraline
Sibutramine
- Withdrawn globally due to the increased incidence of serious, non-fatal cardiovascular events [97]
Slimax
- Extract of several plants including
- Zingiber officinale
- Bofutsushosan [96]
SNS - sypmatický nerovový systém
- Involved in the control of proliferation and differentiation
- Apoptosis of white adipocytes [78]
- Stimulation of sympathetic nerves
- Has no main effect on glucose uptake, utilization and lipogenesis in WAT [78]
- Increased sympathetic tone
- Slow down proliferation and differentiation in white tissue fat
- Might also enhance apoptosis in WAT [78]
- Increased proliferation and differentiation BAT
- Possibly a reduction of brown adipocytes apoptosis
- Leading to higher thermogenic capacity [78]
SNS innervation of BAT
- Blood vessels
- Directly on adipocytes
- Each brown adipocyte receives one or more nerve endings [78]
- ß-adrenergic receptor subtype
- Only one present
- Lipolysis [78]
- Always activated when the sympathetic drive increases [78]
Flos Sophorae
- Significant decrease in body fat [96]
Svalovina a pohybová aktivita
Tělesná výchova ve školách
- The evidence that PE frequency has decreased is itself questionable (Sturm, 2005) [1]
- Has increased (Salmon et al 2003) [1]
- Much evidence suggests that standard PE classes have no appreciable impact on obesity levels (Cawley et al., 2007) [1]
Procházky
- “levels of leisure walking and physical activity were not higher, and rates of obesity were not lower in the non-poor neighborhood with better maintenance, more sidewalks and recreational facilities.” Miles et al (2008) [1]
Fidgeting
Volnočasové aktivity dětí
Cvičení, fitness
Sedavá práce
Literatura:
[1] Ten Putative Contributors to the Obesity Epidemic. URL < www.ncbi.nlm.nih.gov/pmc/articles/PMC2932668/?tool=pmcentrez >
Anorexigenní vlivy
Podnět sytosti
- Z analyticko-regulačního centra v hypotalamu a okolních jader
- Do pocitu potěšení v limbickém systému a orbitofrontální korové oblasti
- Vedle potěšení z jídla regulují významně stav nálady
- Potěšení z jídla
- Stav nálady [5]
Leptin
Tamoxifen
- Regulatable Raf system
- Expressed in 3T3-L1 preadipocytes
- Exposure to tamoxifen
- Causes a 14-fold activation of ERK within 15-30 min
- Results in approximately 2-fold increase in HSL activity
- Differentiated 3T3-L1 cells expressing the regulatable Raf
- Exposed to tamoxifen
- 2-fold increase in lipolysis is observed [13]
- Tamoxifen exposure
- Activation of ERK within 15-30 min
- Approximately 2-fold increase in HSL activity + lipolysis [77]
- Substrate of activated ERK
- ERK consensus phosphorylation sites in HSL identified
- Ser(600) as the site phosphorylated by active ERK
- S600A HSL expressed in 3T3-L1 cells expressing the regulatable Raf
- Tamoxifen treatment fails to increase its activity [77]
- Activation of the ERK pathway
- Appears to be able to regulate adipocyte lipolysis by
- Phosphorylating HSL on Ser(600)
- Increasing the activity of HSL [77]
Topiramate
Triac
- Better agonist than T3 for the TRbeta isoform
- 10–50 more potent than T3 in stimulating the adrenergic increases of UCP1 and D2
- Down-regulates LPL mRNA in the same fashion
- Potent thermogenic agent
- In equimolar dosages, was more potent than T3 in rats in the
- Stimulation of UCP-1
- LPL
- Reducing leptin
- Low doses of Triac induced in adipocyte culture
- Ectopic expression of UCP-1 in inguinal WAT (Medina-Gomez et al., 2008)- in “beige/brite” adipocytes
- Low doses of Triac
- Induce UCP-1 expression in rat inguinal WAT (Medina-Gomez et al., 2008)
Trigonella Foenum-graecum L.
- A significant decrease in appetite [96]
- Chevassus et al 2010 [32] Healthy over wt. male volunteers [n?=?39], double blind
- 1176 mg [approximately 14 mg.kg-1]/d /6 wk
- I: extract
- C: control
- Decrease daily fat consumption
- Non-Sig. effect on wt., Appetite/satiety scores or oxidative parameters
- Decrease in the insulin/glucose ratio [96]
Triiodothyroacetic acid (TRIAC)
- Physiological product of triiodothyronine (T(3)) metabolism
- High affinity for T(3) nuclear receptors
- Control rats were infused with equimolar T(3) or TRIAC doses (0.8 or 4 nmolx100 g body wt(-1) x day(-1)) or exposed for 48 h to cold
- Both T(3) doses and only the highest TRIAC dose
- Inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T(4)) in plasma and tissues [95]
- Lower TRIAC dose
- Marginally inhibited plasma T(4)
- T(3) infusion increased plasma and tissue T(3) in a tissue-specific manner [95]
- Cold exposure or high T(3) doses
- TRIAC increased only in white adipose tissue (WAT)
- Only the lower TRIAC dose activated thermogenesis
- TRIAC, T(3), and cold exposure
- Inhibited leptin secretion and mRNA in WAT
- TRIAC, at low doses
- Induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia [95]
Truncal vagotomy
- Leads to significant reductions in both
- Diet-induced weight gain
- Visceral abdominal fat deposition [12]
Tělesná výchova ve školách
- The evidence that PE frequency has decreased is itself questionable (Sturm, 2005) [1]
- Has increased (Salmon et al 2003) [1]
- Much evidence suggests that standard PE classes have no appreciable impact on obesity levels (Cawley et al., 2007) [1]
Procházky
- “levels of leisure walking and physical activity were not higher, and rates of obesity were not lower in the non-poor neighborhood with better maintenance, more sidewalks and recreational facilities.” Miles et al (2008) [1]
Fidgeting
Volnočasové aktivity dětí
Cvičení, fitness
UCPs
- Overexpression of UCP1 in WAT (Kopecky et al., 1995, 1996)
- Associated to lean phenotypes
- Expression of the UCP mRNA
- Used as a marker of thermogenic capacity
Ectopic UCP1 expression
- Induce obesity resistance
- Ameliorate insulin sensitivity [77]
UCP1 is induced by
- T3 in fetal rat brown adipocytes in primary culture (Guerra et al., 1996)
- Mediated through the TRß 1 isoform (Ribeiro et al., 2001; Martinez De Mena et al., 2010).
The UCP-1 promoter
- CRE sequences (Kozak et al., 1994; Yubero et al., 1998; Rim and Kozak, 2002) in the proximal promoter
Enhancer elements promiscuous for its binding to the UCP-1 promoter:
- TRE elements (Cassard-Doulcier et al., 1994; Rabelo et al., 1995)
- RAREs (Alvarez et al., 1995; Rabelo et al., 1996)
- PPRE in the distal promoter (Teruel et al., 1999)
Negative regulators of UCP-1 expression
- Serum and mitogens that activate c-jun (Yubero et al., 1998)
Vagal de-afferentation
- Leads to a more modest, but significant reduction in visceral abdominal fat [12]
Vagotomy of WAT
- Reduce the insulin-dependent glucose and free fatty acid uptakes in WAT [78]
Vanilloid-1 channels
- Activation of the transient receptor potential vanilloid-1 channels by capsaicin
- Prevents adipogenesis
- A neurogenic mechanism
- Modulates the regulation of fat metabolism
- By transient receptor potential vanilloid-1-sensitive sensory nerves [12]
- A neural pathway enables the selective activation of the central network
- Regulates brown adipose tissue sympathetic nerve activity
- In response to a specific stimulation of gastrointestinal transient receptor potential channels [12]
Weighlevel
The leaves of lady’s mantle, olive and wild mint, the seeds of cumin
- 310 mg tablet-1
- 60 mg A. Vulgaris L.
- 50 mg O. europaea L.
- 20 mg Mentha longiforiaL.
- 25 mg C. cyminum L.
- 7 mg vitamin C
- 148 mg tricalciumphosphate
- Show significant decreases in body weight in studies
- Omar Said et al 2011, Healthy [n?=?66]
- 3 mo
- I: Tablets [before each meal] C: Tablets [before just 3 main meals]
- Reduced BMI
- Sig. and progressive wt. reduction
- No Minor or major adverse effect 90.5?±?1.2 78.5?±?1.4 <0.0005 [96]
Whole grain
- Significant decrease in waist and hip circumferences [96]
- Venn et al 2010, Healthy volunteers [n?=?113] Whole grain
- 2 serves of pulses /d
- 4 serves of wholegrain foods / d
- 18 mo
- No Sig. wt. loss
- Decreased WC 100 ±20.7 94 ±22.8 NS
Xantigen - [brown marine algae fucoxanthin + pomegranate seed oil [PSO]]
- Significant decrease in body weight [96]
- Significant decrease in body fat [96]
- Significant decrease in waist and hip circumferences [96]
- Abidov et al 2010, Obese, premenopausal women [n?=?151], double blind
Yacon syrup
- Show significant decreases in body weight in studies
- Significant decrease in waist and hip circumferences [96]
- Genta et al 2009, Obese & slightly dyslipidemic pre-menopausal women, double blind
- 0.29 g and 0.14 g Fructo-oligosaccharides/kg/d/120 d
- Sig. decrease in BW, WC, BMI
- Decrease in fasting serum insulin and HOMA-IR
- Increased defecation frequency and satiety sensation 91.2?±?8.4 76.2?±?6.1a <0.05 [96]
Zvýšená citlivost androgenních receptorů u mužů
Low number of CAG repeats in AR = vyšší citliovst k androgenům
- Independently associated with protective metabolic parameters
- Low body fat mass and plasma insulin [51]
intact AR transcription
- Favors metabolic homeostasis [51]
Overexpression of AR
- Selectively in muscle cells of transgenic male rats
- Increases their lean mass
- Hypertrophy of type IIb muscle fibers
- Associated with increased oxidative metabolism and metabolic rate
- Reduced adipocyte size and adipose tissue mass [51]