A rare human variant that disrupts GPR10 signalling causes weight gain in mice.
A rare human variant that disrupts GPR10 signalling causes weight gain in mice.
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DOI：
10.1038/s41467-023-36966-3
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发表时间：
2023-03-15
影响因子：
16.6
通讯作者：
Farooqi, I. Sadaf
中科院分区：
文献类型：
--
作者：
Talbot, Fleur;Feetham, Claire H.;Mokrosinski, Jacek;Lawler, Katherine;Keogh, Julia M.;Henning, Elana;de Oliveira, Edson Mendes;Ayinampudi, Vikram;Saeed, Sadia;Bonnefond, Amelie;Arslan, Mohammed;Yeo, Giles S. H.;Froguel, Philippe;Bechtold, David A.;Adamson, Antony;Humphreys, Neil;Barroso, Ines;Luckman, Simon M.;Farooqi, I. Sadaf
脑表达的G蛋白偶联受体-10 （GPR10）的破坏导致动物肥胖。在这里，我们在严重肥胖和体重控制正常的人群中发现了GPR10的多种罕见变异。这些变异损害细胞中的配体结合和G蛋白依赖的信号传导。在肥胖个体中发现的GPR10变体功能缺失的转基因小鼠，由于能量消耗减少而不是食物摄入增加，体重增加过多。这一证据支持GPR10在人体能量稳态中的作用。靶向治疗GPR10可能是一种有效的减肥策略。脑表达受体GPR10参与小鼠能量稳态。在这里，作者发现了严重肥胖人群中罕见的GPR10功能缺失变异，并在小鼠模型中表明其中一种变异会导致肥胖，这表明未来的研究可以探索GPR10作为减肥治疗的潜在靶点。
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. The brain-expressed receptor GPR10 is involved in energy homeostasis in mice. Here the authors identify rare loss of function variants in GPR10 in people with severe obesity and showed that one of these variants causes obesity when modelled in mice, suggesting that future studies could explore GPR10 as a potential target for weight-loss therapy.
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影响因子：
14.9
作者：
Ghoussaini M;Mountjoy E;Carmona M;Peat G;Schmidt EM;Hercules A;Fumis L;Miranda A;Carvalho-Silva D;Buniello A;Burdett T;Hayhurst J;Baker J;Ferrer J;Gonzalez-Uriarte A;Jupp S;Karim MA;Koscielny G;Machlitt-Northen S;Malangone C;Pendlington ZM;Roncaglia P;Suveges D;Wright D;Vrousgou O;Papa E;Parkinson H;MacArthur JAL;Todd JA;Barrett JC;Schwartzentruber J;Hulcoop DG;Ochoa D;McDonagh EM;Dunham I
通讯作者：
Dunham I
影响因子：
29
作者：
Dodd GT;Worth AA;Nunn N;Korpal AK;Bechtold DA;Allison MB;Myers MG Jr;Statnick MA;Luckman SM
通讯作者：
Luckman SM
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
25
作者：
Lawrence, CB;Celsi, F;Luckman, SM
通讯作者：
Luckman, SM
DOI：
10.1016/j.bbrc.2007.09.016
发表时间：
2007-11-23
影响因子：
3.1
作者：
Bjursell, Mikael;Lenneras, Maria;Bohlooly-Y, Mohammad
通讯作者：
Bohlooly-Y, Mohammad