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

Nat Commun. 2023 Mar 15;14(1):1450. doi: 10.1038/s41467-023-36966-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Receptors, G-Protein-Coupled
  • PRLHR protein, human