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

• Published in: Biochemistry (Moscow) Vol. 87; no. 11; pp. 1252 - 1259
• Main Authors: Tanyanskiy, Dmitry A., Shavva, Vladimir S., Dizhe, Ella B., Oleinikova, Galina N., Lizunov, Alexey V., Nekrasova, Ekaterina V., Mogilenko, Denis A., Larionova, Ekaterina E., Orlov, Sergey V., Denisenko, Alexander D.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-11-2022; Springer Nature B.V
• Subjects: Adiponectin; Adiponectin - genetics; Adiponectin - metabolism; Adipose tissue; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; APOA1 gene; Apolipoprotein A; Apolipoprotein A-I - genetics; Apolipoproteins; Atherogenesis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Energy metabolism; Gene Expression; Hep G2 Cells; Hepatocytes; Hepatoma; Humans; Kinases; Life Sciences; Liver X receptors; Liver X Receptors - genetics; Medicin och hälsovetenskap; Microbiology; Peroxisome proliferator-activated receptors; PPAR alpha - genetics; PPAR alpha - metabolism; Receptors; Receptors, Adiponectin - genetics; Receptors, Adiponectin - metabolism; siRNA; nuclear receptors; adiponectin; AMPK; apolipoprotein A-1; hepatocytes
• ISSN: 0006-2979; 1608-3040; 1608-3040
• DOI: 10.1134/S0006297922110049

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.