Exp Clin Endocrinol Diabetes 2009; 117(8): 400-405
DOI: 10.1055/s-0028-1102918
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Fat and Cholesterol Diet Induced Lipid Metabolic Disorders and Insulin Resistance in Rabbit

H. Zheng1 , 2 , C. Zhang1 , W. Yang2 , Y. Wang3 , Y. Lin1 , P. Yang1 , Q. Yu1 , J. Fan1 , 4 , E. Liu1
  • 1Laboratory Animal Center, Xi’an Jiaotong University School of Medicine, Xi’an, China
  • 2Department of Geriatrics, The Second Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, China
  • 3Department of Endocrine, The Second Hospital of Xi’an Jiaotong University School of Medicine, Xi’an, China
  • 4Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan
Further Information

Publication History

received 05.10.2007 first decision 09.01.2008

accepted 24.10.2008

Publication Date:
19 March 2009 (online)

Abstract

Background: Lipid disorder has been found to result in insulin resistance (IR). IR often is associated with other cardiovascular risk factors. However, the pathogenesis of human IR is not completely understood.

Methods: The present study was designed to examine if rabbits were fed with a diet containing high fat and high-cholesterol diet (HFCD) could develop lipid disorder and subsequently IR. Male Japanese white rabbits were fed either a normal chow diet or HFCD for 20 weeks. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured. To evaluate glucose metabolism, we performed an intravenous glucose tolerance test. In addition, we compared adipose tissue accumulation and aortic atherosclerosis lesions in HFCD-fed rabbits with those in control rabbits.

Results: In HFCD-fed rabbits there was an increase in plasma levels of TC and TG as well as visceral adipose tissue accumulation. Severe aortic atherosclerotic lesions were found in HFCD-fed rabbits. Although there were no differences in body weight, plasma insulin and blood pressure between the two groups, HFCD-fed rabbits showed higher insulin IR index compared to control rabbits.

Conclusion: Our results showed that HFCD induced IR, increased adipose accumulation and atherosclerotic lesions in rabbits, suggesting that the HFCD-fed rabbits can serve as a model for the research on human IR and lipid metabolism abnormalities.

References

  • 1 Bergman RN, Finegood DT, Ader M. Assessment of insulin sensitivity in vivo.  Endocr Rev. 1985;  6 45-86
  • 2 Carroll JF, Dwyer TM, Grady AW. et al . Hypertension, cardiac hypertrophy, and neurohumoral activity in a new animal model of obesity.  Am J Physiol. 1996;  271 373-378
  • 3 Diniz YS, Faine LA, Galhardi CM. et al . Monosodium glutamate in standard and high-fiber diets: metabolicsyndrome and oxidative stress in rats.  Nutrition. 2005;  21 749-755
  • 4 Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome.  Lancet. 2005;  365 1415-1428
  • 5 Fan J, Watanabe T. Transgenic rabbits as therapeutic protein bioreactors and human disease models.  Pharmacol Ther. 2003;  99 261-282
  • 6 Hotamisligil GS, Peraldi P, Budavari A. et al . IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha-and obesity-induced insulin resistance.  Science. 1996;  271 665-668
  • 7 Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.  Science. 1993;  259 87-91
  • 8 Isomaa B, Almgren P, Tuomi T. et al . Cardiovascular morbidity and mortality associated with the metabolic syndrome.  Diabetes Care. 2001;  24 683-689
  • 9 Kagota S, Yamaguchi Y, Tanaka N. et al . Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome.  Life Sci. 2006;  78 1187-1196
  • 10 Kawai T, Ito T, Ohwada K. et al . Hereditary postprandial hypertriglyceridemic rabbit exhibits insulin resistance and central obesity: a novel model of metabolic syndrome.  Arterioscler Thromb Vasc Biol. 2006;  26 2752-2757
  • 11 Kearney MT, Duncan ER, Kahn M. et al . Insulin resistance and endothelial cell dysfunction: studies in mammalian models.  Exp Physiol. 2008;  93 158-163
  • 12 Kitajima S, Morimoto M, Liu E. et al . Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits.  Diabetologia. 2004;  47 1202-1209
  • 13 Koike T, Liang J, Wang X. Overexpression of lipoprotein lipase in transgenic Watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity.  J Biol Chem. 2004;  279 7521-7529
  • 14 Lakka HM, Laaksonen DE, Lakka TA. et al . The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.  JAMA. 2002;  288 2709-2716
  • 15 Lerman LO, Chade AR, Sica V. et al . Animal models of hypertension: an overview.  J Lab Clin Med. 2005;  146 160-173
  • 16 Liang J, Liu E, Yu Y. et al . Macrophage metalloelastase accelerates the progression of atherosclerosis in transgenic rabbits.  Circulation. 2006;  113 1993-2001
  • 17 Liu E, Kitajima S, Higaki Y. et al . High lipoprotein lipase activity increases insulin sensitivity in transgenic rabbits.  Metabolism. 2005;  54 132-138
  • 18 Ma LJ, Mao SL, Taylor KL. et al . Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1.  Diabetes. 2004;  53 336-346
  • 19 Maeda N, Shimomura I, Kishida K. et al . Diet-induced insulin resistance in mice lacking adiponectin/ACRP30.  Nat Med. 2002;  8 731-737
  • 20 Marchesini G, Brizi M, Morselli-Labate AM. et al . Association of non-alcoholic fatty liver disease with insulin resistance.  Am J Med. 1999;  107 450-455
  • 21 Masuzaki H, Paterson J, Shinyama H. et al . A transgenic model of visceral obesity and the metabolic syndrome.  Science. 2001;  294 2166-2170
  • 22 Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances.  Ann N Y Acad Sci. 1999;  892 146-154
  • 23 Medina-Gomez G, Vidal-Puig A. Gateway to the metabolic syndrome.  Nat Med. 2005;  11 602-603
  • 24 Mondon CE, Dolkas CB, Oyama J. Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity.  Am J Physiol. 1981;  240 482-488
  • 25 Okamoto Y, Kihara S, Ouchi N. et al . Adiponectin reduces athero-sclerosis in apolipoprotein E-deficient mice.  Circulation. 2002;  106 2767-2770
  • 26 Olefsky JM. The effects of spontaneous obesity on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.  J Clin Invest. 1976;  57 842-851
  • 27 Patrick L. Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine.  Altern Med Rev. 2002;  7 276-291
  • 28 Randle PJ, Garland PB, Hales CN. et al . The glucose-fatty acid cycle: its role in insulin sensitivityand the metabolic disturbances of diabetes mellitus.  Lancet. 1963;  13 785-789
  • 29 Russell JC, Proctor SD. Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis.  Cardiovasc Pathol. 2006;  15 318-330
  • 30 Samuel VT, Liu ZX, Qu X. et al . Mechanism of hepatic insulin resist-ance in non-alcoholic fatty liver disease.  J Biol Chem. 2004;  279 32345-32353
  • 31 Shiomi M, Ito T, Yamada S. et al . Development of an animal model for spontaneous myocardial infarction (WHHLMI rabbit).  Arterioscler Thromb Vasc Biol. 2003;  23 1239-1244
  • 32 Watanabe Y. Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit).  Atherosclerosis. 1980;  36 261-268
  • 33 Zhang B, Saku K, Hirata K. et al . Quantitative characterization of insulin-glucose response in Watanabe heritable hyperlipidemic and cholesterol-fed rabbits and the effect of cilazapril.  Metabolism. 1994;  43 360-366
  • 34 Zhao S, Chu Y, Zhang C. et al . Diet-induced central obesity and in-sulin resistance in rabbit.  J Anim Physiol Anim Nutr (Berl). 2008;  92 105-111

Correspondence

Dr. E. Liu

Professor and Director

Laboratory Animal Center

Xi’an Jiaotong University School of Medicine

Xi’an 710061

China

Phone: 86/29/8265 70 57

Fax: 86/29/8265 70 57

Email: liuenqi@mail.xjtu.edu.cn

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