title: Alpha-lipoic acid induces adipose triglyceride lipase expression and decreases intracellular lipid accumulation in HepG2 cells.
abstract: Non-alcoholic fatty liver disease can be attributed to the imbalance between lipogenesis and lipolysis in the liver. Alpha-lipoic acid has been shown to activate the 5'-AMP-activated protein kinase (AMPK) signalling pathway and to effectively inhibit the lipogenesis pathway in liver. However, whether alpha-lipoic acid stimulates lipolysis remains unclear. Recently, adipose triglyceride lipase (ATGL) was shown to be responsible for triacylglycerol hydrolase activity in cells. In the present study, we established a fatty liver cell model by incubating HepG2 cells in a high glucose (30mM glucose) and high fat (0.1mM palmitate) medium. We found that the activation of the AMPK signalling pathway induced ATGL protein expression and enhanced lipid hydrolysis. Similarly, treatment of the fatty liver cell model with alpha-lipoic acid reduced intracellular lipid accumulation in HepG2 cells, increased AMPK phosphorylation, and induced ATGL expression. We showed that insulin phosphorylates the transcription factor forkhead box O1 (FOXO1), which regulates ATGL expression and inhibits FOXO1 translocation into the nucleus. In contrast, alpha-lipoic acid dephosphorylated FOXO1 and reversed the nuclear exclusion of FOXO1. These data suggest that alpha-lipoic acid can effectively ameliorate intracellular lipid accumulation and induce ATGL expression through the FOXO1/ATGL pathway in liver cells. Thus, alpha-lipoic acid may be a potential therapeutic agent for treating fatty liver disease.
authors: Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taiwan.
authors: Yung-Ting
authors: YT
authors: Kuo
authors: Ting-Han
authors: TH
authors: Lin
authors: Wei-Lu
authors: WL
authors: Chen
authors: Horng-Mo
authors: HM
authors: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D000217:Acyltransferases
chemical_list: D055372:AMP-Activated Protein Kinases; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D005947:Glucose; D007328:Insulin; D008049:Lipase; D056564:Sirtuin 1; D008063:Thioctic Acid; C085126:FOXO1 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C447939:SIRT1 protein, human