Background: The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats.
Methods: Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment.
Results: High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA-IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF-α and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition.
Conclusions: Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance.
1. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011;378:804–14.
2. Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 2002:10:97–104.
3. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–31.
4. Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V, et al. High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 2011;57:611–24.
5. Patton HM, Yates K, Unalp-Arida A, Behling CA, Huang TT, Rosenthal P, et al. Association between metabolic syndrome and liver histology among children with nonalcoholic fatty liver disease. Am J Gastroenterol 2010;105:2093–102.
6. El-Moselhy MA, Taye A, Sharkawi SS, El-Sisi SF, Ahmed AF. The antihyperglycemic effect of curcumin in high fat diet fed rats. Role of TNF-α and free fatty acids. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 2011;49:1129–40.
7. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, et al. Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PloS One 2012;7:e28784.
8. Hsu SC, Huang CJ. Reduced fat mass in rats fed a high oleic acid-rich safflower oil diet is associated with changes in expression of hepatic PPARalpha and adipose SREBP-1c-regulated genes. J Nutr 2006;136:1779–85.
9. Na LX, Zhang YL, Li Y, Liu LY, Li R, Kong T, et al. Curcumin improves insulin resistance in skeletal muscle of rats. Nutr Metab Cardiovasc Dis 2011;21:526–33.
10. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–19.
11. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75.
12. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.
13. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103–11.
14. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497–509.
15. Zaman M-Q, Leray V, Le Bloc’h J, Thorin C, Ouguerram K, Nguyen P. Lipid profile and insulin sensitivity in rats fed with high-fat or high-fructose diets. Br J Nutr 2011;106:S206–10.
16. Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology 2007;132:2169–80.
17. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–808.
18. Dong S, Zhao S, Wu Z, Yang J, Xie X, Yu B, et al. Curcumin promotes cholesterol efflux from adipocytes related to PPARgamma-LXRalpha-ABCA1 passway. Mol Cell Biochem 2011;358:281–5.
19. Gonzales AM, Orlando RA. Curcumin and resveratrol inhibit nuclear factor-kappa B-mediated cytokine expression in adipocytes. Nutr Metab 2008;5:17.
20. Wang SL, Li Y, Wen Y, Chen YF, Na LX, Li ST, et al. Curcumin, a potential inhibitor of up-regulation of TNF-alpha and IL-6 induced by palmitate in 3T3-L1 adipocytes through NF-kappaB and JNK pathway. Biomed Environ Sci 2009;22:32–9.
21. Rösen P, Nawroth PP, King G, Möller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diab Metab Res Rev 2001;17:189–212.
22. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23:599–622.
23. Wolff SP, Dean RT. Glucose autoxidation and protein modification. The potential role of “autoxidative glycosylation” in diabetes. Biochem J 1987;245:243–50.
24. Selvi NM. Curcumin attenuates oxidative stress and activation of redox-sensitive kinases in high fructose- and high-fat-fed male Wistar rats. Sci Pharm 2015;83:1–16.
25. Dinkova-Kostova AT, Talalay P. Relation of structure of curcumin analogs to their potencies as inducers of phase 2 detoxification enzymes. Carcinogenesis 1999;20:911–14.
26. Kolterman OG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. J Clin Invest 1980;65:1272–84.
27. Draznin B. Molecular mechanisms of insulin resistance: serine phosphorylation of insulin receptor substrate-1 and increased expression of p85α the two sides of a coin. Diabetes 2006;55:2392–7.
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