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

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

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number1450
JournalNature Communications
Issue number1
Publication statusPublished - 15 Mar 2023


  • Animals
  • Energy Metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Obesity/genetics
  • Receptors, G-Protein-Coupled/genetics
  • Signal Transduction
  • Weight Gain/genetics


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