title: Leptin activates hepatic 5'-AMP-activated protein kinase through sympathetic nervous system and α1-adrenergic receptor: a potential mechanism for improvement of fatty liver in lipodystrophy by leptin.
abstract: BACKGROUND
  AMPK activation promotes glucose and lipid metabolism.
  
  
  RESULTS
  Hepatic AMPK activities were decreased in fatty liver from lipodystrophic mice, and leptin activated the hepatic AMPK via the α-adrenergic effect.
  
  
  CONCLUSIONS
  Leptin improved the fatty liver possibly by activating hepatic AMPK through the central and sympathetic nervous systems.
  
  
  CONCLUSIONS
  Hepatic AMPK plays significant roles in the pathophysiology of lipodystrophy and metabolic action of leptin. Leptin is an adipocyte-derived hormone that regulates energy homeostasis. Leptin treatment strikingly ameliorates metabolic disorders of lipodystrophy, which exhibits ectopic fat accumulation and severe insulin-resistant diabetes due to a paucity of adipose tissue. Although leptin is shown to activate 5'-AMP-activated protein kinase (AMPK) in the skeletal muscle, the effect of leptin in the liver is still unclear. We investigated the effect of leptin on hepatic AMPK and its pathophysiological relevance in A-ZIP/F-1 mice, a model of generalized lipodystrophy. Here, we demonstrated that leptin activates hepatic AMPK through the central nervous system and α-adrenergic sympathetic nerves. AMPK activities were decreased in the fatty liver of A-ZIP/F-1 mice, and leptin administration increased AMPK activities in the liver as well as in skeletal muscle with significant reduction in triglyceride content. Activation of hepatic AMPK with A769662 also led to a decrease in hepatic triglyceride content and blood glucose levels in A-ZIP/F-1 mice. These results indicate that the down-regulation of hepatic AMPK activities plays a pathophysiological role in the metabolic disturbances of lipodystrophy, and the hepatic AMPK activation is involved in the therapeutic effects of leptin.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto University Hospital, 54 Shogoin Kawahara-cho, Kyoto 606-8507, Japan.
authors.forename: Licht
authors.initials: L
authors.lastname: Miyamoto
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aotani
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamamoto-Kataoka
authors.forename: Takeru
authors.initials: T
authors.lastname: Sakai
authors.forename: Megumi
authors.initials: M
authors.lastname: Aizawa-Abe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005234:Fatty Liver / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000627:therapeutic use; D008060:Lipodystrophy / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000201:enzymology* / Q000378:metabolism
chemical_list: D020738:Leptin; D018340:Receptors, Adrenergic, alpha-1; D055372:AMP-Activated Protein Kinases