title: AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells.
abstract: ANGPTL8 is a liver-derived secretory protein that leads to elevated serum triglyceride and the level of circulating ANGPTL8 is strongly associated with obesity and diabetes. Here we investigated the mechanisms of activation and inhibition of ANGPTL8 expression in hepatocytes. The expression of ANGPTL8 was significantly increased in HepG2 cells exposed to palmitic acid, tunicamycin, or T0901317, and was reversed in cells treated with AICAR. Palmitic acid, tunicamycin, and T0901317 increased LXRα and SREBP-1c mRNA expression. The inhibitory effect of AICAR on the expression of T0901317-induced ANGPTL8 was most strongly evident in cells that were transfected with SREBP-1 siRNA. AICAR increased phosphorylation of PPARα and the effect of AICAR was not observed in cells treated with PPARα inhibitor. Metformin had a similar effect on ANGPTL8 expression to that of AICAR. These data suggest that AMPK can suppress the expression of LXR/SREBP-1 signal-induced ANGPTL8 in HepG2 cells.
authors.affiliation: Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Jinmi
authors.initials: J
authors.lastname: Lee
authors.affiliation: Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Hong
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Park
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Rhee
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Ki-Won
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea. Electronic address: drlwy@hanmail.net.
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D047493:PPAR alpha / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D042682:Angiopoietins; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; D019308:Palmitic Acid; D012265:Ribonucleotides; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D014415:Tunicamycin; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C031143:AICA ribonucleotide
keywords: AMPK; ANGPTL8; Hepatocytes; LXR; PPAR alpha; SREBP-1