ANTI-OBESITY EFFECT OF RESVERATROL IN RATS ON HIGH FAT DIET THROUGH REGULATION OF GENE EXPRESSION OF VISCERAL WHITE ADIPOSE TISSUE

Authors

  • Hoda Mohamed Biochemistry department, faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
  • Mervat Asker
  • Rawia Amin
  • Rana Eissa

Keywords:

Obesity, Visceral white adipose tissue, Calorie restriction, Resveratrol

Abstract

Objective: Obesity is a chronic disease associated with serious health complications including inflammation, insulin resistance, metabolic syndrome, cardiovascular complications and several types of cancers. So this study was carried out to look for effective intervention, especially with its rising prevalence in adults and children and lack of well-tolerated therapy.

Methods: Rats received high-fat diet for four months to induce obesity. Animals which had ≥30 % increase in body weight were selected in this study. Obese rats were treated for 8 w with calorie restriction (25 % food restriction of commercial chow) and/or resveratrol (30 mg/kg/day orally).

Results: Obese rats demonstrated a significant elevation in the body and visceral white adipose tissue (WAT) weight, serum total cholesterol (TC), triacylglycerol (TAG) and low-density lipoprotein cholesterol (LDL-c). Visceral WAT gene expression of fatty acid synthase (FAS) significantly increased. A remarkable decrease in gene expression of peroxisome proliferator-activated receptor gamma (PPARÉ£), lipoprotein lipase (LPL) and silent information regulation 2 homolog 1 (Sirt1) was recorded. The combination significantly decreased body and visceral WAT weights, TC, TAG, LDL-C and FAS mRNA expression and increased adiponectin level, the mRNA expression of PPARÉ£ and Sirt1as compared to individual treatments. While all treatment strategies showed a similar increase in LPL mRNA expression.

Conclusion: Calorie restriction supported with resveratrol has beneficial effects in terms of reducing body weight, and appears to reverse high fat diet-induced dysregulation of expression of the genes responsible for healthy visceral WAT.

Keywords: Obesity, Visceral white adipose tissue, Calorie restriction, Resveratrol.

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References

WHO. Global Health Observatory (GHO) data. Overweight and obesity. Available from: http://www.who.int/ gho/ncd/ risk_factors/overweight_text/en/2014. [Last accessed on 05 Dec 2015].

Haslam DW, James WP. Obesity. Lancet 2005;366:1197-209.

Adnyana I, Sukandar E, Yuniarto A, Finna S. Anti-obesity effect of the pomegranate leaves ethanol extract (Punicagranatuml.) in high-fat diet induced mice. Int J Pharm Pharm Sci 2014;6:626-31.

Koster A, Stenholm S, Alley DE, Kim LJ, Simonsick EM, Kanaya AM, et al. Body fat distribution and inflammation among obese older adults with and without metabolic syndrome. Obesity (Silver Spring) 2010;18:2354-61.

Haas B, Schlinkert P, Mayer P, Eckstein N. Targeting adipose tissue. Diabetol Metab Syndr 2012;4:43.

Chung JH, Manganiello V, Dyck JR. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol 2012;22:546-54.

Ndiaye M, Philippe C, Mukhtar H, Ahmad N. The grape antioxidant resveratrol for skin disorders: promise, prospects, and challenges. Arch Biochem Biophys 2011;508:164-70.

Abete I, Goyenechea E, Zulet MA, Martinez JA. Obesity and metabolic syndrome: potential benefit from specific nutritional components. Nutr Metab Cardiovasc Dis 2011;21 Suppl 2: B1-15.

Chachay VS, Kirkpatrick CM, Hickman IJ, Ferguson M, Prins JB, Martin JH. Resveratrol--pills to replace a healthy diet? Br J Clin Pharmacol 2011;72:27-38.

Cheung BM. Drug treatment for obesity in the post-sibutramine era. Drug Saf 2011;34:641-50.

Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA. The adverse effect of combination of chronic psychosocial stress and high-fat diet on hippocampus-dependent memory in rats. Behav Brain Res 2009;204:117-23.

Ye J. Regulation of PPA Rgamma function by TNF-alpha. Biochem Biophys Res Commun 2008;374:405-8.

Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat-diet-induced obese rats. Lipids Health Dis 2010;9:81.

Kageyama H, Hirano T, Okada K, Ebara T, Kageyama A, Murakami T, et al. Lipoprotein lipase mRNA in white adipose tissue but not in skeletal muscle is increased by pioglitazone through PPAR-gamma. Biochem Biophys Res Commun 2003;305:22-7.

Li L, Yang G, Shi S, Yang M, Liu H, Boden G. The adipose triglyceride lipase, adiponectin, and visfatin are downregulated by tumor necrosis factor-alpha (TNF-alpha) in vivo. Cytokine 2009;45:12-9.

Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 2007;56:901-11.

Liu M, Liu F. Up and down-regulation of adiponectin expression and multimerization: Mechanisms and therapeutic implication. Biochimie 2012;94:2126-30.

Verreth W, De Keyzer D, Pelat M, Verhamme P, Ganame J, Bielicki JK, et al. Weight-loss-associated induction of peroxisome proliferator-activated receptor alpha and peroxisome proliferator activated receptor gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice. Circulation 2004;110:3259-69.

Lim WY, Chia YY, Liong SY, Ton SH, Kadir KA, Husain SN. Lipoprotein lipase expression, serum lipid and tissue lipid deposition in orally-administered glycyrrhizic acid-treated rats. Lipids Health Dis 2009;8:31.

Gil-Campos M, Canete RR, Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 2004;23:963-74.

Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins--novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discovery 2008;7:841-53.

Zhu M, Lee GD, Ding L, Hu J, Qiu G, de Cabo R, et al. Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction. Exp Gerontol 2007;42:733-44.

Sharma AM, Staels B. Review: peroxisome proliferator-activated receptor gamma and adipose tissue--understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab 2007;92:386-95.

Shehzad A, Iqbal W, Shehzad O, Lee YS. Adiponectin: regulation of its production and its role in human diseases. Hormones (Athens) 2012;11:8-20.

Dietze-Schroeder D, Sell H, Uhlig M, Koenen M, Eckel J. Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors. Diabetes 2005;54:2003-11.

Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K, et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density-lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci (Lond) 2002;103:137-42.

Qiu X, Brown KV, Moran Y, Chen D. Sirtuin regulation in calorie restriction. Biochim Biophys Acta 2010;1804:1576-83.

Chakrabarti P, English T, Karki S, Qiang L, Tao R, Kim J, et al. SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. J Lipid Res 2011;52:1693-701.

Canto C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev 2012;64:166-87.

de Ligt M, Timmers S, Schrauwen P. Resveratrol and obesity: can resveratrol relieve metabolic disturbances? Biochim Biophys Acta 2015;1852:1137-44.

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;444:337-42.

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;127:1109-22.

Guarente L. Calorie restriction and sirtuins revisited. Genes Dev 2013;27:2072-85.

Published

01-04-2016

How to Cite

Mohamed, H., M. Asker, R. Amin, and R. Eissa. “ANTI-OBESITY EFFECT OF RESVERATROL IN RATS ON HIGH FAT DIET THROUGH REGULATION OF GENE EXPRESSION OF VISCERAL WHITE ADIPOSE TISSUE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 8, no. 4, Apr. 2016, pp. 378-84, https://journals.innovareacademics.in/index.php/ijpps/article/view/10616.

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