GPR180 reduces adiposity by inhibiting lipogenesis and fatty acid uptake in adipocytes

In this study, we examined the effect of GPR180, a G protein-coupled receptor (GPCR) family member, on lipid metabolism of adipose tissue. We used adeno-associated virus overexpression of Gpr180 in subcutaneous adipose tissue, adipocyte-specific Gpr180 knockout mice and stromal vascular fraction (SVF) cells to explore the role and mechanism of GPR180 in lipid metabolism in adipocytes. Levels of Gpr180 mRNA in subcutaneous and epididymal adipose tissues were significantly reduced in mice fed high-fat diet (HFD). Overexpression of Gpr180 in subcutaneous white adipose tissue (sWAT) improved lipid metabolism and protected mice from HFD-induced obesity. Conversely, adipocyte-specific knockout of Gpr180 exacerbated lipid metabolism disorders induced by HFD. In cultured adipocytes differentiated from SVF cells, GPR180 inhibited lipogenesis and fatty acid (FA) uptake. Collectively, our study reveals that GPR180 functions to suppress lipid accumulation in adipocytes.NEW & NOTEWORTHY This study identifies GPR180 as a novel regulator of lipid metabolism and energy homeostasis. It demonstrates that GPR180 influences adipose tissue function, mitigates high-fat diet-induced obesity, and inhibits lipogenesis. Unique expression patterns and GWAS data linking GPR180 to lipid regulation highlight its systemic role. These findings establish GPR180 as a promising therapeutic target for metabolic disorders, warranting further research to uncover its molecular mechanisms and clinical applications.