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

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.