Dexmedetomidine ameliorates high‐fat diet‐induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice

Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no therapeutic drugs approved for this pathology. Insulin resistance (IR) is implicated both in pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in disease progression from steatosis to nonalcoholic steatohepatitis. In this study, we have characterized effects of an α(2)‐adrenoceptor agonist, dexmedetomidine (DEX), which can alleviate IR in hepatocytes in high‐fat diet (HFD)‐induced NAFLD mice. The NAFLD mice received a daily intraperitoneal administration of DEX (100 μg·kg(‐1)) after 16 days exhibited lower body weight, fewer and smaller fat droplets in the liver, markedly reduced the plasma triglyceride levels, accompanied by improvement of liver damage. This inhibition of lipid accumulation activity in obese mice was associated with a robust reduction in the mRNA and protein expression of the lipogenic enzyme stearyl‐coenzyme A desaturase 1 (SCD1), which was probably mediated by the inhibition of C/EBP β, PPAR γ and C/EBP α through suppressing α (2A) ‐adrenoceptor (α (2A) ‐AR) via negative feedback. Additionally, DEX can also improve IR and inflammation by inhibiting the mitogen‐activated protein kinases (MAPK) and nuclear factor kappa beta (NFκB) signaling pathway in vivo. Our findings implicate that DEX may act as a potential anti‐steatotic drug which ameliorates obesity‐associated fatty liver and improves IR and inflammation, probably by suppressing the expression of SCD1 and the inhibition of MAPK/NFκB pathway and suggest the potential adjuvant use for the treatment of NAFLD.