Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2 liver cells

Abstract

The excessive supply of fatty acids to the liver contributes to hepatic insulin resistance and endoplasmic reticulum (ER) stress associated with obesity or type 2 diabetes mellitus. Furthermore, excess and/or prolonged ER stress contributes to hepatic cell death deteriorating nonalcoholic fatty liver disease to steatohepatitis. The aim of this study was to investigate the effects of metformin on palmitate-induced ER stress and hepatic insulin resistance in HepG2 cells. Metformin significantly inhibited palmitate-induced cell death and apoptosis via caspase-3 activation. Metformin also blocked the induction of ER stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and regulated serine phosphorylation of IRS-1. Metformin may therefore protect hepatocytes from death induced by saturated fatty acids. These data may also provide a further rationale for exploring the use of metformin in the treatment of non-alcoholic fatty liver disease, revealing its blocking effect for hepatic insulin resistance evoked by saturated fatty acids.

Keywords::

• Metformin
• Palmitate
• Apoptosis
• ER stress
• Insulin resistance

Acknowledgments

Declaration of interest: This study was supported by KRF(Korea Research Foundation, 2007-314-E00111, 2007-531-E00015) and KOSEF for the Biofood Research Program, Ministry of Science & Technology, Republic of Korea. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.