Mechanisms of the influence of adiponectin on apolipoproteins A-1 and B production by human hepatocytes

2021 ◽  
Vol 21 (1) ◽  
pp. 39-45
Author(s):  
Dmitriy A. Tanyanskiy ◽  
Ella B. Dizhe ◽  
Galina N. Oleinikova ◽  
Vladimir S. Shavva ◽  
Aleksandr D. Denisenko

The aim of the study was to find out the mechanisms of the adiponectin effect on apolipoproteins (apo) A-1 and B production by human hepatocytes. Materials and methods. The study was performed on the human hepatoma cell line HepG2. The expression of the apoA-1 gene was evaluated at the mRNA level by quantitative PCR with reverse transcription, and the production of apo B by ELISA method. The activity of lipogenesis was assessed by the inclusion of labeled 14C-acetate in triglycerides, as well as by mRNA expression of lipogenesis genes, and by the estimation of total triglycerides content in cells. To determine the involvement of signaling pathways, the RNA interference method was used. Results. Knockdown of genes, coding the specific receptors, AMP-activated protein kinase, and its regulated transcription factors inhibited adiponectin-dependent stimulation of apoA-1 gene expression in hepatocytes. Adiponectin had no effect on lipogenesis and apo B production under basal conditions, but suppressed these processes induced by the addition of oleate. Conclusion. Adiponectin stimulates the production of apo A-1 in hepatocytes by inducing the transcription of the apoA-1 gene and suppresses the secretion of apo B by affecting lipogenesis. These effects may underlie the effect of adiponectin on lipoproteins metabolism.

2011 ◽  
Vol 34 (4) ◽  
pp. 445-453 ◽  
Author(s):  
Coralie Dumont ◽  
Elisabeth Perdu ◽  
Georges de Sousa ◽  
Laurent Debrauwer ◽  
Roger Rahmani ◽  
...  

1994 ◽  
Vol 303 (2) ◽  
pp. 507-510 ◽  
Author(s):  
J Fandrey ◽  
S Frede ◽  
W Jelkmann

The addition of exogenous H2O2 inhibited hypoxia-induced erythropoietin (Epo) production in the human hepatoma cell line HepG2. Likewise, elevation of endogenous H2O2 levels by the addition of menadione or the catalase inhibitor, aminotriazole, dose-dependently lowered Epo production. The inhibitory effect of exogenous H2O2 on Epo formation could be completely overcome by co-incubation with catalase. When GSH levels in HepG2 cells were lowered, Epo production was more susceptible to H2O2-induced inhibition, indicating that H2O2 might affect thiol groups in regulatory proteins. Endogenous production of H2O2 in HepG2 cells was dependent on the pericellular O2 tension, being lowest under conditions of hypoxia. Our results support the hypothesis that an H2O2-generating haem protein might be part of the O2 sensor that controls Epo production. High H2O2 levels under conditions of normoxia suppress, whereas lower levels in hypoxic cells allow epo gene expression.


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