title: Exenatide improves hepatic steatosis by enhancing lipid use in adipose tissue in nondiabetic rats.
abstract: OBJECTIVE
  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 [HFD-Ex(-) 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(+)].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Masaki
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Inoguchi
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.affiliation: Kosuke Tanaka, Yuko Masaki, Masatake Tanaka, Masayuki Miyazaki, Masaki Kato, Masatoshi Nomura, Kazuhiro Kotoh, Ryoichi Takayanagi, Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D002149:Energy Intake / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D000077270:Exenatide; D015971:Gene Expression Regulation, Enzymologic; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D017208:Rats, Wistar; D013997:Time Factors; D015854:Up-Regulation; D014688:Venoms / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D010455:Peptides; D014688:Venoms; D000077270:Exenatide
keywords: Adipose tissue; Energy expenditure; Exenatide; Glucagon-like peptide-1; Hepatic steatosis; Lipolysis; Nonalcoholic fatty liver disease