Key result
Adiponectin stimulates APOA1 gene expression in hepatoma cells via AdipoR, AMPK, PPARα, and LXR pathways.
Why the study?
Adiponectin increases APOA1 gene expression in hepatocytes, but the underlying mechanisms of this effect remained unexplored.
Adiponectin upregulates APOA1 expression in hepatocytes via a signaling pathway involving AdipoR1/R2, AMPK, PPARα, and LXRs.
May link adiponectin to hepatic APOA1 regulation; leaves open in vivo HDL or CV effects.
Adiponectin is an adipose tissue hormone, participating in energy metabolism and involved in atherogenesis. Previously, it was found that adiponectin increases expression of the APOA1 (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 (PPARα) and liver X receptors (LXRs) in mediating the action of adiponectin on hepatic APOA1 expression in human hepatoma HepG2 cells. The level of APOA1 expression was determined by RT-qPCR and ELISA. We showed that the siRNA-mediated knockdown of genes coding for AdipoR1, AdipoR2, AMPK, PPARα, and LXRα and β prevented adiponectin-induced APOA1 expression in HepG2 cells and demonstrated that interaction of PPARα and LXRs with the APOA1 gene hepatic enhancer is important for the adiponectin-dependent APOA1 transcription. The results of this study point out to the involvement of both types of adiponectin receptors, AMPK, PPARα, and LXRs in the adiponectin-dependent upregulation of the APOA1 expression.
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Tanyanskiy et al. (2022) studied this question. Adiponectin was evaluated on APOA1 expression. Adiponectin stimulated APOA1 gene expression in human hepatoma HepG2 cells via AdipoR1/R2, AMPK, PPARα, and LXRs signaling mechanisms.
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