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

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Talbot, Fleur | Feetham, Claire | Mokrosiński, Jacek | Lawler, Katherine | Keogh, Julia | Henning, Elana | Mendes de Oliveira, Edson | Ayinampudi, Vikram | Saeed, Sadia | Bonnefond, Amélie | Arslan, Mohammed | Yeo, Giles | Froguel, Philippe | Bechtold, David | Adamson, Antony | Humphreys, Neil | Barroso, Inês | Luckman, Simon | Farooqi, I. Sadaf

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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