| First Author | Leeson-Payne A | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 5 | Pages | 1076-1087.e4 |
| PubMed ID | 38653246 | Mgi Jnum | J:349468 |
| Mgi Id | MGI:7639587 | Doi | 10.1016/j.cmet.2024.03.016 |
| Citation | Leeson-Payne A, et al. (2024) Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation. Cell Metab 36(5):1076-1087.e4 |
| abstractText | 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 investigated the role of adiposity-associated orphan G protein-coupled receptor 75 (GPR75) in liver lipid accumulation. We profiled Gpr75 expression and report that it is most abundant in the brain. Next, we generated the first single-cell-level analysis of Gpr75 and identified a subpopulation co-expressed with key appetite-regulating hypothalamic neurons. CRISPR-Cas9-deleted Gpr75 mice fed a palatable western diet high in fat adjusted caloric intake to remain in energy balance, thereby preventing NAFLD. Consistent with mouse results, analysis of whole-exome sequencing data from 428,719 individuals (UK Biobank) revealed that variants in GPR75 are associated with a reduced likelihood of hepatic steatosis. Here, we provide a significant advance in understanding of the expression and function of GPR75, demonstrating that it is a promising pharmaceutical target for NAFLD treatment. |
