Resveratrol reduces chronic inflammation and improves insulin action in the myocardium of high-fat diet-induced obese rats
Palabras clave:
Obesity, Resveratrol, Insulin resistance, InflammationResumen
Objective
To evaluate the effects of resveratrol on insulin signaling and inflammation pathway in the myocardium of high-fat diet-induced obese rats.
Methods
Thirty Wistar rats were divided into a control group (n=10, standard diet), obese group (n=10, high-fat diet), and obese supplemented with resveratrol group (n=10, 20 mg/kg/day) for eight weeks. An insulin tolerance test was performed at the end of the study period “0” (without insulin), 5, 10, 15, 20, 25, and 30 minutes after an intraperitoneal injection of insulin (2 U/kg). Body and epididymal adipose tissue were weighed. Fragments of the myocardium were extracted for Western blot analyses of insulin pathway and proinflammatory molecules.
Results
Resveratrol increased the rate of glucose disappearance, phosphorylation of the insulin receptor, insulin receptor substrate 1, and protein kinase B; and reduced expression of tumor necrosis factor alpha and of the moleculesinvolved in proinflammatory signal transduction, namely Ikappa B kinase and nuclear factor kappa B complex. The results also suggest that higher insulin sensitivity and lower levels of proinflammatory molecules occurred regardless of weight and epididymal adipose tissue loss.
Conclusion
Resveratrol increases insulin action and reduces inflammatory molecules in the myocardium.
Citas
De Ferranti S, Mozaffarian D. The perfect storm: Obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008; 54(6):945-55. doi: 10.1373/clinchem.2007.100156
Wing RR, Matthews KA, Kuller LH, Meilahn EN, Plantinga P. Waist to hip ratio in middle-aged women: Associations with behavioral and psychosocial factors and with changes in cardiovascular risk factors. Arterioscler Thromb. 1991; 11(5):1250-7. doi: 10.1161/01.ATV.11.5.1 250
Wellman NS, Friedberg B. Causes and consequences of adult obesity: Health, social and economic impacts in the United States. Asia Pac J Clin Nutr. 2002; 11(Suppl 8):S705-9. doi: 10.1046/j.1440-60 47.11.s8.6.x
Duflou J, Virmani R, Rabin I, Burke A, Farb A, Smialek J. Sudden death as a result of heart disease in morbid obesity. Am Heart J. 1995; 130(2):306-13. doi: 10.1016/0002-8703(95)90445-X
Utriainen T, Takala T, Luotolahti M, Rönnemaa T, Laine H, Ruotsalainen U, et al. Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM. Diabetologia. 1998; 41(5):555-9. doi: 10.1007/s001250050946
De Souza CT, Frederico MJ, da Luz G, Cintra DE, Ropelle ER, Pauli JR, et al. Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4α pathway in insulin resistant mice. J Physiol. 2010; 588(pt12):2239-53. doi: 10.1113/ jphysiol.2009.183996
Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001; 414(6865):799-806. doi: 10.1038/414799a
White MF. The IRS-signaling system: A network of docking proteins the mediate insulin action. Mol Cell Biochem. 1998; 182(1-2):3-11. doi: 10.1023/ A:1006806722619
Saad MJ, Folli F, Kahn JA, Kahn CR. Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats. J Clin Invest. 1993; 92(4):2065-72. doi: 10.1172/JCI116803
Shepherd PR, Navé BT, Siddle K. Insulin activates glycogen synthase by a novel PI3-kinase/p70s6k dependent pathway in 3T3-L1 adipocytes. Biochem Soc Trans. 1995; 23(2):202. doi: 10.1042/bst023 202s
Datta SR, Brunet A, Greenberg ME. Cellular survival: A play in three Akts. Genes Dev. 1999; 13(22): 2905-27.
De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, et al. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinol. 2005; 146(10):4192-9. doi: 10.1210/ en.2004-1520
Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes. Nutr Metab. 2008; 5:17. doi: 10.1186/1743-7075-5-17
Luz G, Silva S, Marques S, Luciano TF, De Souza CT. Suplementação de ácidos graxos poli-insaturados ômega-3 e melhora da ação da insulina e da inflamação em fígado de camundongos. Rev Nutr. 2012; 25(5):621-30. doi: 10.1590/S1415-52732 012000500007
Soleas GJ, Diamandis EP, Goldberg DM. The world of resveratrol. Adv Exp Med Biol. 2001; 492(1): 159-82. doi:10.1007/978-1-4615-1283-7_13
Robich MP, Osipov RM, Nezafat R, Feng J, Clements RT, Bianchi C, et al. Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation. 2010; 122(Suppl 11):S142-9. doi: 10.1161/ CIRCULATIONAHA.109.920132
Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets. 2005; 16(5):251-60. doi: 10.1080/095 37100400020591
Kang W, Hong HJ, Guan J, Kim DG, Yang EJ, Koh G, et al. Resveratrol improves insulin signaling in a tissue-specific manner under insulin-resistant conditions only: In vitro and in vivo experiments in rodents. Metabolism. 2012; 61(3):424-33. doi: 10.1016/j.metabol.2011.08.003
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006; 444(7117):337-42. doi: 10.1038/nature05354
Chen S, Li J, Zhang Z, Li W, Sun Y, Zhang Q, et al. Effects of resveratrol on the amelioration of insulin resistance in KKAy mice. Can J Physiol Pharmacol. 2012; 90(2):237-42. doi: 10.1139/y11-123
Rocha KK, Souza GA, Ebaid GX, Seiva FR, Cataneo AC, Novelli EL. Resveratrol toxicity: Effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food Chem Toxicol. 2009; 47(6):1362-7. doi: 10.1016/j.fct.20 09.03.010
Després JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006; 444(7121): 881-7. doi: 10.1038/nature05488
Deng J, Hsieh P, Huang J, Lu L, Hung L. Activation of estrogen receptor is crucial for resveratrol stimulating muscular glucose uptake via both insulin-dependent and -independent pathways. Diabetes. 2008; 57(7):1814-23. doi: 10.2337/ db07-1750
Movahed A, Nabipour I, Lieben Louis X, Thandapilly SJ, Yu L, Kalantarhormozi M, et al. Antihyperglycemic effects of short term resveratrol supplementation in type 2 diabetic patients. Evid Based Complement Alternat Med. 2013; 2013:851267. doi: 10.1155/20 13/851267
Louis XL, Thandapilly SJ, MohanKumar SK, Yu L, Taylor CG, Zahradka P, et al. Treatment with low dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats. J Nutr Biochem. 2012; 23(9):1163-9. doi: 10.1016/ j.jnutbio.2011.06.010
Goh KP, Lee HY, Lau DP, Supaat W, Chan YH, Koh A FY. Effects of resveratrol in patients with type 2 diabetes Mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int J Sport Nutr Exerc Metab. 2013; [Epub ahead of print].
Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012; 148(3):421-33. doi: 10.1016/j.cell.2012.01.017
Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. 2006; 4(2):31. doi: 10.1371/journal.pbio.00 40031 29. Lee JH, Song MY, Song EK, Kim EK, Moon WS, Han MK, et al. Overexpression of SIRT1 protects pancreatic beta-cells against cytokine toxicity by suppressing the nuclear factor-kappaB signaling pathway. Diabetes. 2009; 58(2):344-51. doi: 10.2337/db07-1795
Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004; 429(6993):771-6. doi: 10.1038/ nature02583
Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, et al. Calorie restriction like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011; 14(5):612-22. doi: 10.1016/j.cmet.2011. 10.002
Do GM, Jung UJ, Park HJ, Kwon EY, Jeon SM, McGregor RA, et al. Resveratrol ameliorates diabetes-related metabolic changes via activation of AMP-activated protein kinase and its downstream targets in db/db mice. Mol Nutr Food Res. 2012; 56(8):1282-91. doi: 10.1002/mnfr. 201200067
Csiszar A. Anti-inflammatory effects of resveratrol: possible role in prevention of age-related cardiovascular disease. NY Acad Sci. 2011; 1215: 117-22. doi: 10.1111/j.1749-6632.2010.0 5848.x
Zhu X, Liu Q, Wang M, Liang M, Yang X, Xu X, et al. Activation of SIRT1 by resveratrol inhibits TNF-á induced inflammation in fibroblasts. PLoS One. 2011; 6(11):e27081. doi: 10.1371/journal.pone. 0027081
Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, et al. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab. 2010; 298(3):19-28. doi: 10.1152/ajpendo.00417.2009
Ungvari ZI, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith KE, et al. Increased mitochondrial H2 O2 production promotes endothelial NF-êB activation in aged rat arteries. Am J Physiol Heart Circ Physiol. 2007; 293(1):H37-47. doi: 10.1152/ajpheart.013 46.2006
Mohora M, Vîrgolici B, Paveliu F, Lixandru D, Muscurel C, Greabu M. Free radical activity in obese patients with type 2 diabetes Mellitus. Rom J Intern Med. 2006; 44(1):69-78.
Avila PR, Marques SO, Luciano TF, Vitto MF, Engelmann J, Souza DR, et al. Resveratrol and fish oil reduce catecholamine-induced mortality in obese rats: Role of oxidative stress in the myocardium and aorta. Br J Nutr. 2013; 110(9):1580-90. doi: 10.1017/S000711451300092
Gao F, Gao E, Yue TL, Ohlstein EH, Lopez BL, Christopher TA, et al. Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: The roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation. 2002; 105(12):1497-502. doi: 10.11 61/01.CIR.0000012529.00367.0F
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Derechos de autor 2023 Thaís Fernandes LUCIANO, Schérolin de Oliveira MARQUES, Bruno Luiz da Silva PIERI, Daniela Roxo de SOUZA, Fabio Santos de LIRA, Cláudio Teodoro de SOUZA
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
