| Title: | Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation |
| Journal: | Cell Metabolism |
| Published: | 18 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38653246/ |
| DOI: | https://doi.org/10.1016/j.cmet.2024.03.016 |
Publication 9863
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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 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.</p>
19 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 32974 | Rare, functionally validated, nonsense and missense mutations and human anthropometric and metabolic traits |
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