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

doi:10.1038/s41467-023-36966-3

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 journal › Article › peer-review

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.

Original language	English
Article number	1450
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36966-3
Publication status	Published - 15 Mar 2023

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-023-36966-3

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Talbot, F., Feetham, C. H., Mokrosiński, J., Lawler, K., Keogh, J. M., Henning, E., Mendes de Oliveira, E., Ayinampudi, V., Saeed, S., Bonnefond, A., Arslan, M., Yeo, G. S. H., Froguel, P., Bechtold, D. A., Adamson, A., Humphreys, N., Barroso, I., Luckman, S. M., & Farooqi, I. S. (2023). A rare human variant that disrupts GPR10 signalling causes weight gain in mice. Nature Communications, 14(1), Article 1450. https://doi.org/10.1038/s41467-023-36966-3

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title = "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.",

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

author = "Fleur Talbot and Feetham, {Claire H.} and Jacek Mokrosi{\'n}ski and Katherine Lawler and Keogh, {Julia M.} and Elana Henning and {Mendes de Oliveira}, Edson and Vikram Ayinampudi and Sadia Saeed and Am{\'e}lie Bonnefond and Mohammed Arslan and Yeo, {Giles S. H.} and Philippe Froguel and Bechtold, {David A.} and Antony Adamson and Neil Humphreys and In{\^e}s Barroso and Luckman, {Simon M.} and Farooqi, {I. Sadaf}",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = mar,

day = "15",

doi = "10.1038/s41467-023-36966-3",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

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Talbot, F, Feetham, CH, Mokrosiński, J, Lawler, K, Keogh, JM, Henning, E, Mendes de Oliveira, E, Ayinampudi, V, Saeed, S, Bonnefond, A, Arslan, M, Yeo, GSH, Froguel, P, Bechtold, DA , Adamson, A, Humphreys, N, Barroso, I, Luckman, SM & Farooqi, IS 2023, 'A rare human variant that disrupts GPR10 signalling causes weight gain in mice', Nature Communications, vol. 14, no. 1, 1450. https://doi.org/10.1038/s41467-023-36966-3

TY - JOUR

T1 - A rare human variant that disrupts GPR10 signalling causes weight gain in mice

AU - Talbot, Fleur

AU - Feetham, Claire H.

AU - Mokrosiński, Jacek

AU - Lawler, Katherine

AU - Keogh, Julia M.

AU - Henning, Elana

AU - Mendes de Oliveira, Edson

AU - Ayinampudi, Vikram

AU - Saeed, Sadia

AU - Bonnefond, Amélie

AU - Arslan, Mohammed

AU - Yeo, Giles S. H.

AU - Froguel, Philippe

AU - Bechtold, David A.

AU - Adamson, Antony

AU - Humphreys, Neil

AU - Barroso, Inês

AU - Luckman, Simon M.

AU - Farooqi, I. Sadaf

PY - 2023/3/15

Y1 - 2023/3/15

N2 - 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.

AB - 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.

KW - Animals

KW - Energy Metabolism

KW - Humans

KW - Mice

KW - Mice, Transgenic

KW - Obesity/genetics

KW - Receptors, G-Protein-Coupled/genetics

KW - Signal Transduction

KW - Weight Gain/genetics

U2 - 10.1038/s41467-023-36966-3

DO - 10.1038/s41467-023-36966-3

M3 - Article

C2 - 36922513

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1450

ER -

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

Abstract

Keywords

UN SDGs

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