Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation.
Cell Metab
; 36(5): 1076-1087.e4, 2024 May 07.
Article
em En
| MEDLINE
| ID: mdl-38653246
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
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Hepatopatia Gordurosa não Alcoólica
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Camundongos Endogâmicos C57BL
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Metab
Ano de publicação:
2024
Tipo de documento:
Article