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: Jinmi Lee, Seok-Woo Hong, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 414 Pg. 148-55 (Oct 15 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26254015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiopoietins
• Hydrocarbons, Fluorinated
• Liver X Receptors
• NR1H3 protein, human
• Orphan Nuclear Receptors
• PPAR alpha
• Ribonucleotides
• Sterol Regulatory Element Binding Protein 1
• Sulfonamides
• T0901317
• Tunicamycin
• Palmitic Acid
• Aminoimidazole Carboxamide
• AMP-Activated Protein Kinases
• AICA ribonucleotide

Topics

• AMP-Activated Protein Kinases (metabolism)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Angiopoietins (genetics, metabolism)
• Hep G2 Cells
• Hepatocytes (drug effects, metabolism)
• Humans
• Hydrocarbons, Fluorinated (pharmacology)
• Liver X Receptors
• Orphan Nuclear Receptors (genetics)
• PPAR alpha (metabolism)
• Palmitic Acid (pharmacology)
• Phosphorylation (drug effects)
• Ribonucleotides (pharmacology)
• Signal Transduction (drug effects)
• Sterol Regulatory Element Binding Protein 1 (genetics)
• Sulfonamides (pharmacology)
• Tunicamycin (pharmacology)