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

Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Munechika Enjoji, Makoto Nakamuta, Masaki Kato, Masatoshi Nomura, Toyoshi Inoguchi, Kazuhiro Kotoh, Ryoichi Takayanagi

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18 Citations (Scopus)

Abstract

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 4 wk, 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.

Original languageEnglish
Pages (from-to)2653-2663
Number of pages11
JournalWorld Journal of Gastroenterology
Volume20
Issue number10
DOIs
Publication statusPublished - Mar 14 2014

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Tanaka, K., Masaki, Y., Tanaka, M., Miyazaki, M., Enjoji, M., Nakamuta, M., Kato, M., Nomura, M., Inoguchi, T., Kotoh, K., & Takayanagi, R. (2014). Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats. World Journal of Gastroenterology, 20(10), 2653-2663. https://doi.org/10.3748/wjg.v20.i10.2653