Abstract
Hepatic steatosis, a common liver disorder, can progress to severe conditions such as nonalcoholic steatohepatitis and cirrhosis. While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild-type (WT) mice. When fed a high-fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate/protein kinase A/AMP-activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1-α, and their target β-oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD-fed mice, potentially by influencing sterol regulatory element-binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the in vivo role of MOR23 in hepatic steatosis development.