Zhu Ziming, Yang Yaxu, Sun Lijun, Zhang Yunhua, Han Xue, Luo Chao, Yin Yue, Zhang Weizhen
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, People's Republic of China.
Am J Physiol Endocrinol Metab. 2025 Mar 1;328(3):E410-E419. doi: 10.1152/ajpendo.00178.2024. Epub 2025 Feb 10.
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 in subcutaneous adipose tissue, adipocyte-specific knockout mice and stromal vascular fraction (SVF) cells to explore the role and mechanism of GPR180 in lipid metabolism in adipocytes. Levels of mRNA in subcutaneous and epididymal adipose tissues were significantly reduced in mice fed high-fat diet (HFD). Overexpression of in subcutaneous white adipose tissue (sWAT) improved lipid metabolism and protected mice from HFD-induced obesity. Conversely, adipocyte-specific knockout of 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. 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.
在本研究中，我们检测了G蛋白偶联受体（GPCR）家族成员GPR180对脂肪组织脂质代谢的影响。我们利用腺相关病毒在皮下脂肪组织中过表达、脂肪细胞特异性基因敲除小鼠以及基质血管成分（SVF）细胞，来探究GPR180在脂肪细胞脂质代谢中的作用及机制。高脂饮食（HFD）喂养的小鼠皮下和附睾脂肪组织中该基因的mRNA水平显著降低。皮下白色脂肪组织（sWAT）中该基因的过表达改善了脂质代谢，并保护小鼠免受HFD诱导的肥胖。相反，脂肪细胞特异性敲除该基因加剧了HFD诱导的脂质代谢紊乱。在由SVF细胞分化而来的培养脂肪细胞中，GPR180抑制脂肪生成和脂肪酸（FA）摄取。总的来说，我们的研究表明GPR180具有抑制脂肪细胞脂质积累的功能。本研究确定GPR180为脂质代谢和能量稳态的新型调节因子。它表明GPR180影响脂肪组织功能，减轻高脂饮食诱导的肥胖，并抑制脂肪生成。GPR180独特的表达模式以及将其与脂质调节联系起来的全基因组关联研究（GWAS）数据突出了其系统性作用。这些发现确立了GPR180作为代谢紊乱有前景的治疗靶点，值得进一步研究以揭示其分子机制和临床应用。
