Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPAR α, and LXRs Signaling Mechanisms

AbstractAdiponectin is an adipose tissue hormone, participating in energy metabolism and involved in atherogenesis. Previously, it was found that adiponectin increases expression of theAPOA1 (apolipoprotein A-1) gene in hepatocytes, but the mechanisms of this effect remained unexplored. Our aim was to investigate the role of adiponectin receptors AdipoR1/R2, AMP-activated protein kinase (AMPK), nuclear peroxisome proliferator-activated receptor alpha (PPAR α) and liver X receptors (LXRs) in mediating the action of adiponectin on hepaticAPOA1 expression in human hepatoma HepG2 cells. The level ofAPOA1 expression was determined by RT-qPCR and ELISA. We showed that the siRNA-mediated knockdown of genes coding for AdipoR1, AdipoR2, AMPK, PPAR α, and LXRα and β prevented adiponectin-inducedAPOA1 expression in HepG2 cells and demonstrated that interaction of PPAR α and LXRs with theAPOA1 gene hepatic enhancer is important for the adiponectin-dependentAPOA1 transcription. The results of this study point out to the involvement of both types of adiponectin receptors, AMPK, PPAR α, and LXRs in the adiponectin-dependent upregulation of theAPOA1 expression.
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research