Olfactory receptors are primarily expressed in nasal olfactory epithelium, but these receptors are also ectopically expressed in diverse tissues. In this study, we investigated the biological functions of Olfr43, a mouse homolog of human OR1A1, in cultured hepatocytes and mice to assess its functionality in lipid metabolism. Olfr43 was expressed in mouse hepatocytes, and Olfr43 activation by a known ligand, (-)-carvone, stimulated cAMP response element-binding protein (CREB) activity. In ligand-receptor binding studies using site-directed mutagenesis, (-)-carvone binding required two residues, M257 and Y258, in Olfr43. In the mouse study, oral administration of (-)-carvone for 5 weeks in high-fat diet-fed mice improved energy metabolism, including reductions in hepatic steatosis and adiposity, and improved glucose and insulin tolerance. In mouse livers and cultured mouse hepatocytes, Olfr43 activation simulated the CREB-hairy and enhancer of split 1 (HES1)-peroxisome proliferator-activated receptor (PPAR)-γ signaling axis, leading to a reduction in hepatic triglyceride accumulation in the mouse liver. Thus, long-term administration of (-)-carvone reduces hepatic steatosis. The knockdown of Olfr43 gene expression in cultured hepatocytes negated these effects of (-)-carvone. In conclusion, an ectopic olfactory receptor, hepatic Olfr43, regulates energy metabolism via the CREB-HES1-PPARγ signaling axis.