Resveratrolün Adipozite Üzerine Etkileri

Sağlık üzerinde yararlı biyolojik etkilere sahip olan resveratrol, son yıllarda araştırmalara en fazla konu olan besin bileşenlerinden biridir. Resveratrol (3,5,4?-trihidroksistilben), metilen köprüsüyle bağlanmış iki aromatik halka içeren polifenolik bir bileşiktir. Sirtuin 1'in aktifleşmesini sağlayan resveratrolün bazı kanser türlerine, iskemiye, infeksiyonlara, kardiyovasküler hastalıklara karşı koruyucu olduğu, platelet agregasyonunu baskıladığı, vazodilatör, antioksidan, antiinflamatuvar, antiviral özellik gösterdiği ifade edilmektedir. Bunlara ek olarak resveratrolün adipogenez, lipogenez, lipoliz, yağ asidi oksidasyonu ve termogenez gibi metabolik yolaklarda da etkilerinin olduğu belirtilmektedir. Başta adipoz dokuda olmak üzere karaciğer ve iskelet kaslarında lipit metabolizması üzerinde rol oynamaktadır. Derleme olarak hazırlanan bu makalede, günümüzün önemli halk sağlığı sorunlarından biri olan obezitenin önlenmesinde veya tedavisinde resveratrolün etkisinin tartışılması amaçlanmıştır

Effects of Resveratrol on Adiposity

Resveratrol, which has beneficial biological effects on health, is one of the most commonly researched food components in recent years. Resveratrol (3,5,4’-trihydroxystilbene) is a polyphenolic compound containing two aromatic rings linked via a methylene bridge. Resveratrol activates sirtuin 1 and it is claimed to be protective against some types of cancer, ischemia, infections, and cardiovascular disease, to inhibit platelet aggregationand to have vasodilator, antioxidant, anti-inflamatory, and antiviral properties. In addition, resveratrol might be involved in metabolic pathways such as adipogenesis, lipogenesis, lipolysis, fatty acid oxidation and thermogenesis. It plays a role in lipid metabolism in the liver, skeletal muscles, and especially in the adipose tissue. In this review article, it is aimed to discuss the effect of resveratrol on the prevention or treatment of obesity, one of the most important public health problems

PDF

___

1. WHO: Obesity, 2016. Available at: http://www.who.int/ topics/obesity/en/. Accessed October 10, 2016.
2. Field AE, Coakley EH, Must A, Spadano JL, Laird N, Dietz WH. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med 2001;161(13):1581-1586.
3. WHO: Obesity and Overweight, 2016. Available at: http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed November 11, 2016.
4. T.C. Sağlık Bakanlığı Sağlık Araştırmaları Genel Müdürlüğü, Hacettepe Üniversitesi Sağlık Bilimleri Fakültesi Beslenme ve Diyetetik Bölümü, Ankara Numune Eğitim ve Araştırma Hastanesi. Türkiye Beslenme ve Sağlık Araştırması (TBSA) 2010: Beslenme Durumu ve Alışkanlıklarının Değerlendirilmesi Sonuç Raporu. Sağlık Bakanlığı Yayın No: 931, Ankara 2014.
5. Watanabe E, Lee JS, Mori K, Kawakubo K. Clustering patterns of obesity-related multiple lifestyle behaviours and their associations with overweight and family environments: a cross-sectional study in Japanese preschool children. BMJ Open 2016;6(11):e012773.
6. Sağlık Bakanlığı, 2015. Sağlık için obezite ile mücadele. Erişim Adresi: [http://www.saglik.gov. tr/TR/belge/1-40258/obezite.html]. Erişim Tarihi: 08/10/2016.
7. Catalgol B, Batirel S, Taga Y, Kartal ON. Resveratrol: French paradox revisited. Front Pharmacology 2012;3:141-158.
8. Pallàs M, Porquet D, Vicente A, Camins A, Sanfeliu C. Resveratrol: New avenues for a natural compound in neuroprotection. Curr Pharma Design 2016;19(38):6726-6731.
9. Signorelli P, Ghidoni R. Resveratrol as an anticancer nutrient: molecular basis, open questions and promises. J Nutr Biochem 2005;16(8):449-466.
10. Langcake P, Pryce RJ. A new class of phytoalexins from grapevines. Experientia 1977;33(2):151–152.
11. Pervaiz S. Resveratrol: From grapevines to mammalian biology. FASEB J 2003;17(14):1975-1985.
12. Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic 1992;43(1):49-52.
13. Bay-Karabulut A. Resveratrol ve etkileri. Turkiye Klinikleri J Med Sci 2008;28(6):166-169.
14. Dixon RA. Natural products and plant disease resistance. Nature 2001;411(6839):843– 847.
15. Regev-Shoshani G, Shoseyov O, Bilkis I, Kerem Z. Glycosylation of resveratrol protects it from enzymic oxidation. Biochem J 2003;374(1):157-163.
16. King RE, Bomser JA, Min DB. Bioactivity of resveratrol. Compreh Rev Food Sci Food Safety 2006;5(3):65-70.
17. Arora MK, Strange RN. Phytoalexin accumulation in groundnuts in response to wounding. Plant Sci 1991;78(2):157-163.
18. Chachay VS, Kirkpatrick CM, Hickman IJ, Ferguson M, Prins JB, Martin JH. Resveratrol--pills to replace a healthy diet?. Br J Clin Pharmacol 2011;72(1):27-38.
19. Counet C, Callemien D, Collin S. Chocolate and cocoa: New sources of trans-resveratrol and trans-piceid. Food Chem 2006;98(4):649-657.
20. Porte C, Voduc N, Zhang G, Seguin I, Tardiff D, Singhal N, et al. Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 2010;49(7):449-454.
21. Kuhnle G, Spencer JPE, Chowrimootoo G, Schroeter H, Debnam ES, Srai SKS, et al. Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 2000;272(1):212-217.
22. Henry-Vitrac C, Desmoulière A, Girard D, Mérillon JM, Krisa S. Transport, deglycosylation, and metabolism of trans-piceid by small intestinal epithelial cells. Eur J Nutr 2006;45(7):376-382.
23. Walle T, Hsieh F, Delegge MH, Oatis JE, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 2004;32(12):1377-1382.
24. Bertelli AA, Giovannini L, Stradi R, Bertelli A, Tillement JP. Plasma, urine and tisue levels of trans and cis-resveratrol (3,4’,5-trihydroxystilbene) after shortterm or prolonged administration of red wine to rats. Int J Tissue React 1995;18(2-3):67-71.
25. Goldberga DM, Yanb J, Soleasab GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem 2003;36(1):79-87.
26. Knutson MD, Leeuwenburgh C. Resveratrol and novel potent activators of SIRT1: Effects on aging and agerelated diseases. Nutrition Rev 2008;66(10):591–596.
27. Cottart CH, Nivet-Antoine V, Laguillier-Morizot C, Beaudeux JL. Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res 2010;54(1):7-16.
28. Boocock DJ, Faust GES, Patel KR, Schinas AM, Brown WA, Ducharme MP, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 2007;16(6):1246- 1252.
29. Aguirre L, Fernández-Quintela A, Arias N, Portillo MP. Resveratrol: Anti-obesity mechanisms of action. Molecules 2014;19(11):18632-18655.
30. Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 2006;7(12):885-896.
31. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006;4(4):263–273.
32. Kwon JY, Seo SG, Yue S, Cheng JX, Lee KW, Kim KH. An inhibitory effect of resveratrol in the mitotic clonal expansion and insulin signaling pathway in the early phase of adipogenesis. Nutr Res 2012;32(8):607-616.
33. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 2005;280(17):17187–17195.
34. Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci 2007;104(17):7217-7222.
35. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, De Oliveira RM, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPARgamma. Nature 2004;429:771–776.
36. Picard F, Guarente L. Molecular links between aging and adipose tissue. Int J Obes 2005;29:36–39.
37. Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol 2011;89(11):793– 799.
38. Kang NE, Ha AW, Kim JY, Kim WK. Resveratrol inhibits the protein expression oftranscription factors related adipocyte differentiation and the activity of matrix metalloproteinase in mouse fibroblast 3T3-L1 preadipocytes. Nutr Res Pract 2012;6:499–504.
39. Hu P, Zhao L, Chen J. Physiologically achievable doses of resveratrol enhance 3T3-L1 adipocyte differentiation. Eur J Nutr. 2014;doi:10.1007/s00394-014-0738-4.
40. Vázquez-Vela ME, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res 2008;39(8):715–728.
41. Wang CS, Hartsuck J, Mcconathy WJ. Structure and functional properties of lipoprotein lipase. Biochim Biophys Acta 1992;1123(1):1–17.
42. Auwerx J, Schoonjans K, Fruchart JC, Staels B. Transcriptional control of triglyceride metabolism: Fibrates and fatty acids change the expression of the LPL and apo C-III genes by activating the nuclear receptor PPAR. Atherosclerosis 1996;124:29–37.
43. Rivera L, Morón R, Zarzuelo A, Galisteo M. Longterm resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009;77(6):1053-1063.
44. Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res 2009;48:275- 297.
45. Rayalam S, Yang JY, Ambati S, Della-Fera MA, Baile CA. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res 2008;22(10):1367-1371.
46. Lasa A, Schweiger M, Kotzbeck P, Churruca I , Simón E, Del Puy Portillo M, et al. Resveratrol regulates lipolysis via adipose triglyceride lipase. J Nutr Biochem 2012;23(4):379–384.
47. Isken F, Klaus S, Petzke KJ, Loddenkemper C, Pfeiffer AF, Weickert MO. Impairment of fat oxidation under high- vs. low-glycemic index diet occurs before the development of an obese phenotype. Am J Physiol Endocrinol Metab 2010;298(2): 287–295.
48. Eaton S, Bartlett K, Pourfarzam M. Mammalian mitochondrial beta-oxidation. Biochem J 1996;320(2):345–357.
49. Kerner J, Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta 2000;1486(1):1–17.
50. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006;127(6):1109–1122.
51. Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Churruca I, Portillo MP. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem 2013;141(2):1530–1535.
52. Gómez-Zorita S, Fernández-Quintela A, Macarulla MT, Aguirre L, Hijona E, Bujanda L, et al. Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress. Br J Nutr 2012;107(02):202–210.
53. Ricquier D, Casteilla L, Bouillaud F. Molecular studies of the uncoupling protein. June The FASEB Journal 1991;5(9):2237-2242.
54. Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 2008;3(6):1-10.