| Title: | A rare human variant that disrupts GPR10 signalling causes weight gain in mice |
| Journal: | Nature Communications |
| Published: | 15 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36922513/ |
| DOI: | https://doi.org/10.1038/s41467-023-36966-3 |
| URL: | https://www.nature.com/articles/s41467-023-36966-3.pdf |
Publication 11204
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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.</p>
19 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 53821 | Genetic basis of body weight regulation in the population: comparison with extreme phenotypes of severe obesity and persistent thinness |
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