J Korean Endocr Soc.  2008 Feb;23(1):27-34. 10.3803/jkes.2008.23.1.27.

Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells

Affiliations
  • 1Department of Internal Medicine, Keimyung University School of Medicine, Korea.
  • 2Department of Internal Medicine, Kyungpook National University School of Medicine, Korea.

Abstract

BACKGROUND: Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression.
METHODS
We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK).
RESULTS
Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation.
CONCLUSION
The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed.

Keyword

alpha-lipoic acid; insulin resistance; non-alcoholic fatty liver disease; SREBP-1c

MeSH Terms

AMP-Activated Protein Kinases
Biosynthetic Pathways
Blotting, Western
Carcinoma, Hepatocellular
Cell Line
Fatty Liver
Hep G2 Cells
Humans
Insulin
Insulin Resistance
Liver
Models, Animal
Phosphorylation
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
Thioctic Acid
Transcription Factors
AMP-Activated Protein Kinases
Fatty Liver
Insulin
RNA, Messenger
Sterol Regulatory Element Binding Protein 1
Thioctic Acid
Transcription Factors
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