摘要：SummaryGpr52 is an orphan G-protein-coupled receptor of unknown physiological function. We found that Gpr52-deficient (Gpr52−/−) mice exhibit leanness associated with reduced liver weight, decreased hepaticde novolipogenesis, and enhanced insulin sensitivity. Treatment of the hepatoma cell line HepG2 cells with c11, the synthetic GPR52 agonist, increased fatty acid biosynthesis, and GPR52 knockdown (KD) abolished the lipogenic action of c11. In addition, c11 induced the expressions of lipogenic enzymes (SCD1andELOVL6), whereas these inductions were attenuated by GPR52-KD. In contrast, cholesterol biosynthesis was not increased by c11, but its basal level was significantly suppressed by GPR52-KD. High-fat diet (HFD)-induced increase in hepatic expression ofPparg2and its targets (Scd1andElovl6) was absent inGpr52−/−mice with alleviated hepatosteatosis. Our present study showed that hepatic GPR52 promotes the biosynthesis of fatty acid and cholesterol in a ligand-dependent and a constitutive manner, respectively, and Gpr52 participates in HFD-induced fatty acid synthesis in liver.Graphical abstractDisplay OmittedHighlights•Hepatosteatosis is inherently an adaptive response to overnutrition to store energy•On the other hand, it can be a pathological condition causing insulin resistance•High-fat diet increases PPARγ2 expression and lipogenesis in liver via GPR52•Gpr52 ablation protects mice from developing hepatosteatosis and insulin resistanceHuman Metabolism; Molecular Biology
