Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats

• Published in: World journal of gastroenterology : WJG Vol. 20; no. 10; pp. 2653 - 2663
• Main Authors: Tanaka, Kosuke, Masaki, Yuko, Tanaka, Masatake, Miyazaki, Masayuki, Enjoji, Munechika, Nakamuta, Makoto, Kato, Masaki, Nomura, Masatoshi, Inoguchi, Toyoshi, Kotoh, Kazuhiro, Takayanagi, Ryoichi
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 14.03.2014
• Subjects: Adipose; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Appetite Regulation - drug effects; Blood Glucose - drug effects; Blood Glucose - metabolism; Diet, High-Fat; Disease Models, Animal; Energy; Energy Intake - drug effects; Energy Metabolism - drug effects; Exenatide; expenditure; Gene Expression Regulation, Enzymologic; Glucag; Lipolysis - drug effects; Lipolysis - genetics; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mitochondria - drug effects; Mitochondria - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - pathology; Original; Oxygen Consumption - drug effects; Peptides - pharmacology; Rats, Wistar; Time Factors; tissue; Up-Regulation; Venoms - pharmacology; Weight Gain - drug effects; Glucagon-like peptide-1; Adipose tissue; Energy expenditure; Nonalcoholic fatty liver disease; Hepatic steatosis; Exenatide; Lipolysis
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i10.2653

AIM:To investigate the metabolic changes in skeletal muscle and/or adipose tissue in glucagon-like peptide-1-induced improvement of nonalcoholic fatty liver disease(NAFLD).METHODS:Male Wistar rats were fed either a control diet(control group)or a high-fat diet(HFD).After 4wk,the HFD-fed rats were subdivided into two groups;one group was injected with exenatide[HFD-Ex(+)group]and the other with saline[HFD-Ex(-)group]every day for 12 wk.The control group received saline and were fed a control diet.Changes in weight gain,energy intake,and oxygen consumption were analyzed.Glucose tolerance tests were performed after 8 wk of treatment.Histological assessments were performed in liver and adipose tissue.RNA expression levels of lipid metabolism related genes were evaluated in liver,skeletal muscle,and adipose tissue.RESULTS:Exenatide attenuated weight gain[HFDEx(-)vs HFD-Ex(+)]and reduced energy intake,which was accompanied by an increase in oxygen consumption and a decrease in the respiratory exchange ratio[HFD-Ex(-)vs HFD-Ex(+)].However,exenatide did not affect glucose tolerance.Exenatide reduced lipid content in the liver and adipose tissue.Exenatide did not affect the expression of lipid metabolism-related genes in the liver or skeletal muscle.In adipose tissue,exenatide significantly upregulated lipolytic genes,including hormone-sensitive lipase,carnitine palmitoyltransferase-1,long-chain acyl-CoA dehydrogenase,and acyl-CoA oxidase 1[HFD-Ex(-)vs HFD-Ex(+)].Exenatide also upregulated catalase and superoxide dismutase 2[HFD-Ex(-)vs HFD-Ex(+)].CONCLUSION:In addition to reducing appetite,enhanced lipid use by exenatide in adipose tissue may reduce hepatic lipid content in NAFLD,most likely by decreasing lipid influx into the liver.