AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells. (15th October 2015)

• Record Type: Journal Article
• Authors: Lee, Jinmi; Hong, Seok-Woo; Park, Se Eun; Rhee, Eun-Jung; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Lee, Won-Young
• Is Part Of: Molecular and cellular endocrinology. Volume 414(2015)
• Page Start: 148
• Page End: 155
• Publication Date: 2015-10-15
• Subjects: ANGPTL8 -- LXR -- SREBP-1 -- AMPK -- PPAR alpha -- Hepatocytes; ANGPTL angiopoietin-like protein -- AMPK AMP-activated protein kinase -- SIRT1 silent mating type information regulation 2 homolog 1 -- NAFLD non-alcoholic fatty liver disease -- TG triglyceride -- PPARα peroxisomal proliferator-activated receptor α -- TD26 TD26 homolog -- RIFL refeeding-induced fat and liver protein -- WAT white adipose tissue -- LPL lipoprotein lipase -- LXRE LXR responsive element -- RXR 9-cis retinoic acid receptor -- PEPCK phosphoenolpyruvate carboxykinase -- G6Pase glucose-6-phosphatase; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.07.031
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: Palmitic acid and tunicamycin increases the expression of hepatic ANGPTL8. The increased expression of ANGPTL8 is mediated by LXR/SREBP-1 signaling. AMPK agonists suppress the expression of ANGPTL8. AMPK induces phosphorylation and activation of PPARα. Inhibition of PPARα attenuates effect of AMPK on controlling of ANGPTL8 expression.