Alpha-lipoic acid induces adipose triglyceride lipase expression and decreases intracellular lipid accumulation in HepG2 cells

Yung Ting Kuo, Ting Han Lin, Wei Lu Chen, Horng Mo Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 (30 mM glucose) and high fat (0.1 mM 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.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalEuropean Journal of Pharmacology
Volume692
Issue number1-3
DOIs
Publication statusPublished - Oct 5 2012

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Keywords

  • 5′-AMP-activated protein kinase (AMPK)
  • Adipose triglyceride lipase (ATGL)
  • Alpha-lipoic acid (ALA)
  • Forkhead box O1 (FOXO1)

ASJC Scopus subject areas

  • Pharmacology

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