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

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Dmitry A. Tanyanskiy^1,2,a*, Vladimir S. Shavva¹, Ella B. Dizhe¹, Galina N. Oleinikova¹, Alexey V. Lizunov^1,3, Ekaterina V. Nekrasova¹, Denis A. Mogilenko¹, Ekaterina E. Larionova¹, Sergey V. Orlov^1,3, and Alexander D. Denisenko^1,2

¹Department of Biochemistry, Institute of Experimental Medicine, 197376 St. Petersburg, Russia

²Department of Fundamental Problems of Medicine and Medical Technologies, St. Petersburg State University, 199034 St. Petersburg, Russia

³Department of Embryology, St. Petersburg State University, 199034 St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received September 19, 2022; Revised September 19, 2022; Accepted October 6, 2022

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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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KEY WORDS: adiponectin, apolipoprotein A-1, hepatocytes, AMPK, nuclear receptors

DOI: 10.1134/S0006297922110049

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