Effect of dexmedetomidine against lipid accumulation in hepatocytes and related mechanism

Abstract:

Objective To investigate the regulatory effect of dexmedetomidine（DEX） on lipid metabolism in hepatocytes and the underlying mechanism.Methods Primary mouse hepatocytes were isolated and then treated with free fatty acids for 24 hours to establish a hepatocyte lipid accumulation model. Primary hepatocytes were treated with DEX separately at concentrations of 200 ng/mL，500 ng/mL，and 1 000 ng/mL for 24 hours，and then were collected for Oil Red O staining to observe the level of lipid accumulation. The expression levels of key lipid metabolism genes in hepatocytes were determined by real-time quantitative PCR and Western blot. The expression of α_2A-adrenoceptors at different time points of DEX treatment was measured by real-time quantitative PCR. The protein expression of associated signaling pathways was determined by Western blot.Results The level of lipid accumulation in primary hepatocytes was significantly reduced after treatment with DEX in a dose-dependent manner. The expression levels of key genes related to fatty acid and triglyceride synthesis（including fatty acid synthase，stearoyl-coenzyme A desaturase 1，and peroxisome proliferator-activated receptor γ） were significantly inhibited（P<0.05）. The expression of α_2A-adrenoceptors was firstly increased and then inhibited. In addition，DEX significantly decreased the phosphorylation levels of P65 and P38 in primary hepatocytes（P<0.05）.Conclusion DEX can reduce lipid accumulation in the liver，which may be related to the activation of α_2A-adrenoceptors and the MAPK/NF-κB signaling pathway.