Neuronal GPR75 deficiency protects against diet-induced obesity in a humanized mouse model.

ABSTRACT: GPR75, a G protein-coupled receptor implicated in human obesity through loss-of-function variants, has emerged as a promising regulator of energy and metabolic homeostasis. To dissect its tissue-specific functions, we generated a humanized floxed Gpr75 mouse model with conditional deletions in the brain and adipose tissue. Mice with brain-specific Gpr75 deletion using Nestin-Cre were resistant to diet-induced obesity, primarily through suppressed food intake and modest increases in energy expenditure. In contrast, adipocyte-specific deletion of Gpr75 had minimal effects on systemic metabolism but modestly enhanced mitochondrial oxygen consumption in brown adipose tissue under cold exposure. Gpr75 expression was up-regulated in key brain regions and down-regulated in white adipose ti

SUBMITTER: Sun XN 

PROVIDER: S-EPMC12829562 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature