title: Liver-specific deletion of the signal transducer and activator of transcription 5 gene aggravates fatty liver in response to a high-fat diet in mice.
abstract: Growth hormone (GH) signal is mediated by signal transducer and activator of transcription 5 (STAT5), which controls hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is clinically associated with a deficiency in GH. This study was performed to understand the role of local STAT5 signaling on hepatic lipid and glucose metabolism utilizing liver-specific STAT5 gene deletion (STAT5 LKO) mice under both normal diet and high-fat diet (HFD) feeding conditions. STAT5 LKO induced hepatic steatosis under HFD feeding, while this change was not observed in mice on normal diet. STAT5 LKO caused hyperglycemia, hyperinsulinemia, hyperleptinemia and elevated free fatty acid and cholesterol concentrations under HFD feeding but induced only hyperglycemia on normal diet. At the molecular level, STAT5 LKO up-regulated the expression of genes involved in lipid uptake (CD36), very low-density lipoprotein receptor (VLDLR), lipogenic stearoyl-CoA desaturase and adipogenic peroxisome proliferator-activated receptor gamma, in both diet groups. In response to HFD feeding, further increases in CD36 and VLDLR expression were found in STAT5 LKO mice. In conclusion, our study suggests that low STAT5 signaling on normal diet predisposes STAT5 LKO mice to early development of fatty liver by hyperglycemia and activation of lipid uptake and adipogenesis. A deficiency in STAT5 signaling under HFD feeding deregulates hepatic and body glucose and lipid metabolism, leading to the development of hepatic steatosis. Our study indicates that low STAT5 signaling, due to low GH secretion, may increase a chance for NAFLD development in elderly people.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea; Institute of GreenBio Science Technology, Pyeungchang-gun, Gangwon-do 232-916, Republic of Korea. Electronic address: mgbaik@snu.ac.kr.
authors.forename: Myunggi
authors.initials: M
authors.lastname: Baik
authors.affiliation: Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Nam
authors.affiliation: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Min Yu
authors.initials: MY
authors.lastname: Piao
authors.affiliation: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Hyeok Joong
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
authors.forename: Seung Ju
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D017353:Gene Deletion; D006128:Growth; D008099:Liver / Q000378:metabolism*; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009929:Organ Size; D050799:STAT5 Transcription Factor / Q000235:genetics*
chemical_list: D050799:STAT5 Transcription Factor
keywords: Fatty liver; Growth hormone; High fat diet; Lipid metabolism; STAT5