英国阿伯丁大学Lora K. Heisler等研究人员合作发现，GPR75缺失可预防非酒精性脂肪肝和体内脂肪堆积。该研究于2024年4月22日在线发表于国际一流学术期刊《细胞—代谢》。

研究人员调查了与脂肪相关的孤儿G蛋白偶联受体75（GPR75）在肝脏脂质积累中的作用。研究人员分析了Gpr75的表达，发现它在大脑中的表达最为丰富。接下来，研究人员首次对Gpr75进行了单细胞水平的分析，并确定了一个与下丘脑关键食欲调节神经元共表达的亚群。用CRISPR-Cas9删除Gpr75的小鼠喂食高脂肪适口的西方饮食，调整热量摄入以保持能量平衡，从而预防非酒精性脂肪肝（NAFLD）。

与小鼠的结果一致，来自428719人（英国生物库）的全外显子组测序数据分析显示，GPR75的变异与肝脂肪变性的可能性降低有关。在此，研究人员对GPR75的表达和功能有了更深入的了解，证明它是治疗NAFLD的一个有望药物靶点。

据悉，全世界大约每4人中就有1人患有NAFLD，但目前还没有治疗这种疾病的药物。

附：英文原文

Title: Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation

Author: Alasdair Leeson-Payne, Jean Iyinikkel, Cameron Malcolm, Brian Y.H. Lam, Nadine Sommer, Georgina K.C. Dowsett, Pablo B. Martinez de Morentin, Dawn Thompson, Alasdair Mackenzie, Raffaella Chianese, Katherine Kentistou, Eugene J. Gardner, John R.B. Perry, Felix Grassmann, John R. Speakman, Justin J. Rochford, Giles S.H. Yeo, Fiona Murray, Lora K. Heisler

Issue&Volume: 2024-04-22

Abstract: Approximately 1 in 4 people worldwide have non-alcoholic fatty liver disease (NAFLD);however, there are currently no medications to treat this condition. This study investigatedthe role of adiposity-associated orphan G protein-coupled receptor 75 (GPR75) in liverlipid accumulation. We profiled Gpr75 expression and report that it is most abundant in the brain. Next, we generated thefirst single-cell-level analysis of Gpr75 and identified a subpopulation co-expressed with key appetite-regulating hypothalamicneurons. CRISPR-Cas9-deleted Gpr75 mice fed a palatable western diet high in fat adjusted caloric intake to remain inenergy balance, thereby preventing NAFLD. Consistent with mouse results, analysisof whole-exome sequencing data from 428,719 individuals (UK Biobank) revealed thatvariants in GPR75 are associated with a reduced likelihood of hepatic steatosis. Here, we provide asignificant advance in understanding of the expression and function of GPR75, demonstratingthat it is a promising pharmaceutical target for NAFLD treatment.

DOI: 10.1016/j.cmet.2024.03.016

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00120-7