Concurrent Exercise Improves Insulin Resistance and Nonalcoholic Fatty Liver Disease by Upregulating PPAR-γ and Genes Involved in the Beta-oxidation of Fatty Acids in ApoE-KO Mice Fed a High-fat Diet

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2019 Jan 7

PMID 30611282

Citations 53

Authors

Fan Zheng

Ying Cai

Affiliations

Soon will be listed here.

Abstract

Objective: To emphasize the mechanism of concurrent exercise effect on lipid disorders in insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD).

Materials And Methods: Twenty male ApoE knockout mice were randomly divided into two groups: HFD group (n = 10) fed a high fat diet, and HFDE group (n = 10) with high-fat diet intervention for 12 weeks and swimming exercise. Other ten healthy male C57BL/6 J mice were fed a normal diet, and included as control group. Retro-orbital blood samples were collected for biochemical analysis. Oil red O staining of liver tissues was performed to confirm the exercise effect. Western blotting was performed to evaluate the expressions of PPAR-γ, CPT-1, MCAD.

Results: The levels of TG, TC, LDL, FFA, FIN, FPG and Homa-IRI in the HFD group were significantly higher than ND group, while these were markedly decreased in the HFDE group compared with HFD group. The Oil Red O staining of liver samples further confirmed the exercise effect on the change of lipid deposition in the liver. Western blotting showed increased expressions of PPAR-γ, CPT-1, MCAD induced by high fat diet were significantly downregulated by exercise.

Conclusion: A concurrent 12-week exercise protocol alleviated the lipid metabolism disorders of IR and NAFLD, probably via PPAR-γ/CPT-1/MCAD signaling.

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References

Straczkowski M, Kowalska I, Kinalski M, Gorski J, Kinalska I . The effect of exercise training on glucose tolerance and skeletal muscle triacylglycerol content in rats fed with a high-fat diet. Diabetes Metab. 2001; 27(1):19-23. View

Gauthier M, Couturier K, Latour J, Lavoie J . Concurrent exercise prevents high-fat-diet-induced macrovesicular hepatic steatosis. J Appl Physiol (1985). 2003; 94(6):2127-34. DOI: 10.1152/japplphysiol.01164.2002. View

Ye J, Iglesias M, Watson D, Ellis B, Wood L, Jensen P . PPARalpha /gamma ragaglitazar eliminates fatty liver and enhances insulin action in fat-fed rats in the absence of hepatomegaly. Am J Physiol Endocrinol Metab. 2003; 284(3):E531-40. DOI: 10.1152/ajpendo.00299.2002. View

Gilde A, van der Lee K, Willemsen P, Chinetti G, van der Leij F, van der Vusse G . Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res. 2003; 92(5):518-24. DOI: 10.1161/01.RES.0000060700.55247.7C. View

Neuschwander-Tetri B, Brunt E, Wehmeier K, Oliver D, Bacon B . Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003; 38(4):1008-17. DOI: 10.1053/jhep.2003.50420. View

Estadella D, Oyama L, Damaso A, Ribeiro E, Oller do Nascimento C . Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats. Nutrition. 2004; 20(2):218-24. DOI: 10.1016/j.nut.2003.10.008. View

Park S, Kim B, Yun J, Kim J, Park D, Cho Y . Insulin resistance and C-reactive protein as independent risk factors for non-alcoholic fatty liver disease in non-obese Asian men. J Gastroenterol Hepatol. 2004; 19(6):694-8. DOI: 10.1111/j.1440-1746.2004.03362.x. View

Tous M, Ferre N, Camps J, Riu F, Joven J . Feeding apolipoprotein E-knockout mice with cholesterol and fat enriched diets may be a model of non-alcoholic steatohepatitis. Mol Cell Biochem. 2005; 268(1-2):53-8. DOI: 10.1007/s11010-005-2997-0. View

Hammarstedt A, Andersson C, Rotter Sopasakis V, Smith U . The effect of PPARgamma ligands on the adipose tissue in insulin resistance. Prostaglandins Leukot Essent Fatty Acids. 2005; 73(1):65-75. DOI: 10.1016/j.plefa.2005.04.008. View

10.

Inoue M, Ohtake T, Motomura W, Takahashi N, Hosoki Y, Miyoshi S . Increased expression of PPARgamma in high fat diet-induced liver steatosis in mice. Biochem Biophys Res Commun. 2005; 336(1):215-22. DOI: 10.1016/j.bbrc.2005.08.070. View

11.

Neuschwander-Tetri B . Nonalcoholic steatohepatitis and the metabolic syndrome. Am J Med Sci. 2005; 330(6):326-35. DOI: 10.1097/00000441-200512000-00011. View

12.

Burneiko R, Diniz Y, Galhardi C, Rodrigues H, Ebaid G, Faine L . Interaction of hypercaloric diet and physical exercise on lipid profile, oxidative stress and antioxidant defenses. Food Chem Toxicol. 2006; 44(7):1167-72. DOI: 10.1016/j.fct.2006.01.004. View

13.

Pellieux C, Aasum E, Larsen T, Montessuit C, Papageorgiou I, Pedrazzini T . Overexpression of angiotensinogen in the myocardium induces downregulation of the fatty acid oxidation pathway. J Mol Cell Cardiol. 2006; 41(3):459-66. DOI: 10.1016/j.yjmcc.2006.06.004. View

14.

Zhang Y, Hernandez-Ono A, Siri P, Weisberg S, Conlon D, Graham M . Aberrant hepatic expression of PPARgamma2 stimulates hepatic lipogenesis in a mouse model of obesity, insulin resistance, dyslipidemia, and hepatic steatosis. J Biol Chem. 2006; 281(49):37603-15. DOI: 10.1074/jbc.M604709200. View

15.

Fliegner D, Westermann D, Riad A, Schubert C, Becher E, Fielitz J . Up-regulation of PPARgamma in myocardial infarction. Eur J Heart Fail. 2007; 10(1):30-8. DOI: 10.1016/j.ejheart.2007.11.005. View

16.

Souza-Mello V, Gregorio B, Cardoso-de-Lemos F, de Carvalho L, Aguila M, Mandarim-de-Lacerda C . Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet. Clin Sci (Lond). 2010; 119(6):239-50. DOI: 10.1042/CS20100061. View

17.

Marques C, Motta V, Torres T, Aguila M, Mandarim-de-Lacerda C . Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice. Braz J Med Biol Res. 2010; 43(5):467-75. DOI: 10.1590/s0100-879x2010007500030. View

18.

Boden G . Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011; 18(2):139-43. PMC: 3169796. DOI: 10.1097/MED.0b013e3283444b09. View

19.

Zheng H, Li S, Ma L, Cheng L, Deng C, Chen Z . A novel agonist of PPAR-γ based on barbituric acid alleviates the development of non-alcoholic fatty liver disease by regulating adipocytokine expression and preventing insulin resistance. Eur J Pharmacol. 2011; 659(2-3):244-51. DOI: 10.1016/j.ejphar.2011.03.033. View

20.

Lavoie J, Pighon A . NAFLD, Estrogens, and Physical Exercise: The Animal Model. J Nutr Metab. 2011; 2012:914938. PMC: 3154523. DOI: 10.1155/2012/914938. View