title: 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.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Chonbuk, Republic of Korea.
authors.forename: Do-Sung
authors.initials: DS
authors.lastname: Kim
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Jeong
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Dal-Sik
authors.initials: DS
authors.lastname: Kim
authors.forename: Soo-Wan
authors.initials: SW
authors.lastname: Chae
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Chae
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D047468:Immunoprecipitation; D007328:Insulin / Q000096:biosynthesis; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects*; D019308:Palmitic Acid / Q000009:adverse effects*; D010766:Phosphorylation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D019308:Palmitic Acid; D008687:Metformin; D053148:Caspase 3