Kuo_2012_Eur.J.Pharmacol_692_10

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.