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A rare human variant that disrupts GPR10 signalling causes weight gain in mice.

ABSTRACT: Disruption of brain-expressed G protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identify multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impair ligand binding and G protein-dependent signalling in cells. Transgenic mice harbouring a loss of function GPR10 variant found in an individual with obesity, gain excessive weight due to decreased energy expenditure rather than increased food intake. This evidence supports a role for GPR10 in human energy homeostasis. Therapeutic targeting of GPR10 may represent an effective weight-loss strategy.

SUBMITTER: Talbot F

PROVIDER: S-EPMC10017677 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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A rare human variant that disrupts GPR10 signalling causes weight gain in mice.

Talbot Fleur F Feetham Claire H CH Mokrosiński Jacek J Lawler Katherine K Keogh Julia M JM Henning Elana E Mendes de Oliveira Edson E Ayinampudi Vikram V Saeed Sadia S Bonnefond Amélie A Arslan Mohammed M Yeo Giles S H GSH Froguel Philippe P Bechtold David A DA Adamson Antony A Humphreys Neil N Barroso Inês I Luckman Simon M SM Farooqi I Sadaf IS

Nature communications 20230315 1

Disruption of brain-expressed G protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identify multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impair ligand binding and G protein-dependent signalling in cells. Transgenic mice harbouring a loss of function GPR10 variant found in an individual with obesity, gain excessive weight due to decreased energy expenditure rather than increased food intake. This evidence supports ...[more]

PMID: 36922513

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