title: Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways.
abstract: Fatty liver is common in obese subjects with insulin resistance. Hepatic expression of sterol regulatory element binding protein-1c (SREBP-1c), which plays a major role in hepatic steatosis, is regulated by multiple factors, including insulin, adenosine monophosphate-activated protein kinase (AMPK), liver X receptors (LXRs), and specificity protein 1. Alpha-lipoic acid (ALA), a naturally occurring antioxidant, has been shown to decrease lipid accumulation in skeletal muscle by activating AMPK. Here we show that ALA decreases hepatic steatosis and SREBP-1c expression in rats on a high fat diet or given an LXR agonist. ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant-negative AMPK partially prevented ALA-induced suppression of insulin-stimulated SREBP-1c expression. ALA also inhibited DNA-binding activity and transcriptional activity of both specificity protein 1 and LXR.
  
  
  CONCLUSIONS
  These results show that ALA prevents fatty liver disease through multiple mechanisms, and suggest that ALA can be used to prevent the development and progression of nonalcoholic fatty liver disease in patients with insulin resistance.
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: Ae-Kyung
authors.initials: AK
authors.lastname: Min
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Hyoun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Yong-Deuk
authors.initials: YD
authors.lastname: Kim
authors.forename: Tae-Seung
authors.initials: TS
authors.lastname: Yoon
authors.forename: Byoung Kuk
authors.initials: BK
authors.lastname: Jang
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Hwang
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Hueng-Sik
authors.initials: HS
authors.lastname: Choi
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008113:Liver Neoplasms; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008055:Lipids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014280:Triglycerides; D008063:Thioctic Acid; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases