title: Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet.
abstract: OBJECTIVE
  Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model.
  
  
  METHODS
  Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions.
  
  
  RESULTS
  STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation.
  
  
  CONCLUSIONS
  STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.
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. mgbaik@snu.ac.kr.|Institute of Green Bio Science Technology, Gangwon-do, Pyeungchang-gun, 232-916, Republic of Korea. mgbaik@snu.ac.kr.
authors.forename: Myunggi
authors.initials: M
authors.lastname: Baik
authors.affiliation: Bioneer Corporation, 8-11 Munpyengseoro, Daedeok-gu, Daejeon, 306-220, Republic of Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Lee
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 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 Molecular Biotechnology, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Trang Hoa
authors.initials: TH
authors.lastname: Nguyen
authors.affiliation: Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000172:deficiency* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018955:CD36 Antigens; D012333:RNA, Messenger; D011973:Receptors, LDL; D050799:STAT5 Transcription Factor; C036053:VLDL receptor; D008071:Lipoprotein Lipase; D005947:Glucose
keywords: Hepatic lipid accumulation; Intramyocellular lipid accumulation; Lipid and glucose metabolism; STAT5 muscle deletion