TY - JOUR
T1 - Adiponectin Stimulates Apolipoprotein A-1 Gene Expression in HepG2 Cells via AMPK, PPARα, and LXRs Signaling Mechanisms
AU - Tanyanskiy, Dmitry A.
AU - Shavva, Vladimir S.
AU - Dizhe, Ella B.
AU - Oleinikova, Galina N.
AU - Lizunov, Alexey V.
AU - Nekrasova, Ekaterina V.
AU - Mogilenko, Denis A.
AU - Larionova, Ekaterina E.
AU - Orlov, Sergey V.
AU - Denisenko, Alexander D.
N1 - Publisher Copyright:
© 2022, Pleiades Publishing, Ltd.
PY - 2022/11
Y1 - 2022/11
N2 - Abstract: 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.
AB - Abstract: 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.
KW - AMPK
KW - adiponectin
KW - apolipoprotein A-1
KW - hepatocytes
KW - nuclear receptors
UR - http://www.scopus.com/inward/record.url?scp=85142145041&partnerID=8YFLogxK
U2 - 10.1134/S0006297922110049
DO - 10.1134/S0006297922110049
M3 - Article
C2 - 36509728
AN - SCOPUS:85142145041
SN - 0006-2979
VL - 87
SP - 1252
EP - 1259
JO - Biochemistry (Moscow)
JF - Biochemistry (Moscow)
IS - 11
ER -