Effect of Low-calorie Diet Supplemented with Genistein on Lipid Profile, Blood Glucose and Proinflammatory Biomarkers in Diet-induced Obese Rats


1 M.Sc. of Nutrition. Department of Nutrition, Faculty of Paramedicine, Nutrition Research Center, Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Assistant Professor of Nutrition.Department of Nutrition, Faculty of Paramedicine, Nutrition Research Center, Jundishapur University of Medical Sciences, Ahvaz, Iran.

3 Associate Professor of Nutrition. Department of Nutrition, Faculty of Paramedicine, Diabetes Research Center, Jundishapur University of Medical Sciences, Ahvaz, Iran.


Background and Objective: Obesity is a worldwide public health problem that results in comorbidities including diabetes, dyslipidemia, coronary artery disease and some types of cancer. It seems that soy isoflavones can improve obesity and reverse subsequent metabolic disorders. In this study, we assessed the effect of restriction of calorie supplemented with genistein on diet-induced obese rats.
Subjects and Methods: Thirty rats obesed with high fat diet were divided randomly into 3 experimental groups (n=10) as follows: group 1: low calorie diet supplemented with 50mg/kgbw genistein, group2: low calorie diet supplemented with Dimethyl Sulphoxide (DMSO) (as vehicle) and group3: obese control rats with ad libitum access to standard food. After 4 weeks, fasting blood samples were collected and analyzed for biochemical analysis.
Results: The results showed that administration of genistein in conjunction with low calorie diet can synergistically improve triglyceride (p=0.005), VLDL (p=0.005), total cholesterol(p=0.002) and LDL-C (P=0.003) and increase HDL-C (p=0.001) but has no effect on body weight and proinflammatory biomarkers (resistin and CRP). Restriction of calorie also resulted in the decrease of glucose level, TG, TC, LDL, proinflammatory biomarker (CRP) and increase in HDL-C (p<0.05) but has no effect on resistin level.
Conclusion: It seems that administration of genistein with restriction of calorie is useful for improvement of hyperlipidemia in obese hyperlipidemic patients.
Sci Med J 2012;11(1):57-67


1-Lazar MA. How obesity causes diabetes: not a tall tale. Science 2005;307:373–5.
2-Zimmermann-Belsing T, Feldt-Rasmussen U. Obesity: the new worldwide epidemic threat to general health and our complete lack of effective treatment. Endocrinology 2004;145:1501–2.
3-Wozniak SE, Gee LL, Wachtel MS, Frezza EE.. Adipose tissue: The new endocrine organ? A review article. Dig Dis Sci 2009;54:1847–56.
4-Kopelman PG. Obesity as a medical problem. Nature 2000;404:635–643.
5-Astrup A, Dyerberg J, Selleck M, Stender S. Nutrition transition and its relationship to the development of obesity and related chronic diseases. Obes Rev 2008; 9 Suppl 1:48–52.
6-Cope MB, Erdman JW Jr, Allison DB. The potential role of soyfoods in weight and adiposity reduction: an evidence-based review. Obes Rev 2008;9:219–35.
7-Orgaard A, Jensen L. The effects of soy isoflavones on obesity. Exp Biol Med (Maywood) 2008;233:1066–80.
8-Rayalam S, Della-Fera MA, Baile CA. Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem 2008;19:717–26.
9-Naaz A, Yellayi S, Zakroczymski MA, Bunick D, Doerge DR, Lubahn DB, et al. The soy isoflavone genistein decreases adipose deposition in mice. Endocrinology 2003;144:3315–20.
10-Reinli K, Block G. Phytoestrogen content of foods--a compendium of literature values. Nutr Cancer 1996;26:123–48.
11-Dang ZC. Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: mechanisms of action. Obes Rev 2009;10:342–9.
12-Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr 2003;133:1238–43.
13-Kim S, Shin HJ, Kim SY, Kim JH, Lee YS, Kim DH, et al. Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARalpha. Mol Cell Endocrinol 2004;220:51–8.
14-McCrindle BW. Hyperlipidemia in children. Thromb Res 2006;118:49-58.
15-Polkowski K, Mazurek AP. Biological properties of genistein. A review of  in vitro and in vivo data. Acta pol pharm 2000;57:135-55.
16-Banz WJ, Davis J, Peterson R, Iqbal MJ. Gene expression and adiposity are modified by soy protein in male Zucker diabetic fatty  rats. Obes Res 2004;12:1907–13.
17-Jones KL, Harty J, Roeder MJ, Winters TA, Banz WJ. In vitro effects of soy phytoestrogens on rat L6 skeletal muscle cells. J Med Food 2005;8:327–31.
18-Guo Y, Wu G, Su X, Yang H, Zhang H. Antiobesity action of a daidzein derivative on male obese mice induced by a high-fat diet. Nut Research 2009:29(9);656-663.
19-Kirk EA, Sutherland P, Wang SA, Chait A, LeBoeuf RC. Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. J Nutr 1998;128:954–9.
20-Owen AJ, Roach PD, Abbey M. Regulation of low-density lipoprotein receptor activity by estrogens and phytoestrogens in a HepG2 cell model. Ann Nutr Metab 2004;48:269–75.
21-Mullen E, Brown RM, Osborne TF, Shay NF. Soy isoflavones affect sterol regulatory element binding proteins (SREBPs) and SREBP-regulated genes in HepG2 cells. J Nutr  2004;134:2942–7.
22-Shin ES, Lee HH, Cho SY, Park HW, Lee SJ, Lee TR. Genistein downregulates SREBP-1 regulated gene expression by inhibiting sit-1  protease expression in HepG2 cells. J Nutr 2007;137:1127–31.
23-Amani R, Zand Moghaddam A, Baghdadchi J. Effects of soy protein isoflavones on serum lipids, lipoprotein profile and serum glucose of hypercholesterolemic rabbits. Int J Endocrinol Metab 2005;2:87-92.
24-Cederroth CR, Vinciguerra M, Gijnovci A, Kuhne F, Klein M, Cederroth M, et al. Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism. Diabetes 2008;57:1176–85.
25-Lee JS. Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sci 2006;79:1578–84.
26-Adeghate E. An update on the biology and physiology of resistin. Cell Mol Life Sci. 2004;61: 2485–96.
27-Chen SW, Zhang HM, Zhang LS, Feng XF. Effects of soy isoflavone on gene expression of resistin in insulin-resistance rats. Sichuan Da Xue Xue Bao Yi Xue Ban 2006;37:717-20.
28-Selvin E, Paynter NP, Erlinger TP. The effect of weight loss on C-reactive Protein: a systematic review. Arch Intern Med 2007;167:31-9.
29-Yildiz MF, Kumru S, Godekmerdan A, Kutlu S. Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women. Int J Gynaecol Obstet 2005;90:128-33.
30-Jenkins D, Kendall CW, Connelly PW, Jackson CJ, Parker T, Faulkner D, et al. Effects of high-and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism 2002;51:919-24.