The role of GPRC6A agonists in satiety

GPRC6A 激动剂在饱腹感中的作用

• 批准号: BB/I001816/1
• 负责人: Kevin Murphy
• 金额: $ 52.8万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI001816%2F1
• 关键词: role; GPRC6A; agonists; satiety

Recent research has highlighted the importance of nutrient sensing in the regulation of food intake and body weight. Meals and diets high in protein have a well characterised satiating effect. However, the mechanisms by which high levels of protein inhibit food intake are largely unknown. Proteins are digested to form amino acids in the gut. We have found that specific amino acids which bind to an amino acids-sensing receptor called GPRC6A reduce food intake when injected into the blood stream of rats and mice. These amino acids appear to act on the brain, which may in response reduce the release of an appetite-increasing hormone called ghrelin from the stomach. We now aim to determine the specific mechanisms behind the effects of these amino acids on food intake and determine whether they form part of the system that regulates food intake and body weight on a day to day basis. Determining the role of GPRC6A in food intake may facilitate the design of foods or drugs designed to comabt obesity.

最近的研究强调了营养传感在食物摄入和体重调节中的重要性。富含蛋白质的膳食和饮食具有明显的饱腹感。然而，高水平蛋白质抑制食物摄入的机制在很大程度上尚不清楚。蛋白质在肠道中被消化形成氨基酸。我们发现，当注射到大鼠和小鼠的血流中时，与氨基酸感应受体 GPRC6A 结合的特定氨基酸会减少食物摄入量。这些氨基酸似乎作用于大脑，从而可能减少胃中一种名为胃饥饿素的增进食欲的激素的释放。我们现在的目标是确定这些氨基酸对食物摄入影响背后的具体机制，并确定它们是否构成日常调节食物摄入和体重的系统的一部分。确定 GPRC6A 在食物摄入中的作用可能有助于设计用于对抗肥胖的食物或药物。

项目成果

L-cysteine suppresses ghrelin and reduces appetite in rodents and humans.

• DOI: 10.1038/ijo.2014.172
• 发表时间: 2015-03
• 期刊: INTERNATIONAL JOURNAL OF OBESITY
• 影响因子: 4.9
• 作者: McGavigan, A. K.;O'Hara, H. C.;Amin, A.;Kinsey-Jones, J.;Spreckley, E.;Alamshah, A.;Agahi, A.;Banks, K.;France, R.;Hyberg, G.;Wong, C.;Bewick, G. A.;Gardiner, J. V.;Lehmann, A.;Martin, N. M.;Ghatei, M. A.;Bloom, S. R.;Murphy, K. G.
• 通讯作者: Murphy, K. G.

GPRC6a is not required for the effects of a high-protein diet on body weight in mice.

• DOI: 10.1002/oby.21083
• 发表时间: 2015-06
• 期刊: Obesity (Silver Spring, Md.)
• 作者: Kinsey-Jones JS;Alamshah A;McGavigan AK;Spreckley E;Banks K;Cereceda Monteoliva N;Norton M;Bewick GA;Murphy KG
• 通讯作者: Murphy KG

l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents.

• DOI: 10.1038/ijo.2017.164
• 发表时间: 2017-11
• 期刊: International journal of obesity (2005)
• 作者: Alamshah A;Spreckley E;Norton M;Kinsey-Jones JS;Amin A;Ramgulam A;Cao Y;Johnson R;Saleh K;Akalestou E;Malik Z;Gonzalez-Abuin N;Jomard A;Amarsi R;Moolla A;Sargent PR;Gray GW;Bloom SR;Murphy KG
• 通讯作者: Murphy KG

L-Arginine Increases Postprandial Circulating GLP-1 and PYY Levels in Humans.

L-精氨酸增加了人类的餐后循环GLP-1和PYY水平。

• DOI: 10.1002/oby.22323
• 发表时间: 2018-11
• 期刊: Obesity (Silver Spring, Md.)
• 作者: Amin A;Neophytou C;Thein S;Martin NM;Alamshah A;Spreckley E;Bloom SR;Murphy KG
• 通讯作者: Murphy KG

Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss.

• DOI: 10.1016/j.xcrm.2022.100810
• 发表时间: 2022-11-15
• 期刊: CELL REPORTS MEDICINE
• 影响因子: 14.3
• 作者: Hope, David C. D.;Hinds, Charlotte E.;Lopes, Tatiana;Vincent, Matthew L.;V. Shrewsbury, Jed;Yu, Arthur T. C.;Davies, Iona;Scott, Rebecca;Jones, Ben;Murphy, Kevin G.;Minnion, James S.;Sardini, Alessandro;Carling, David;Lutz, Thomas A.;Bloom, Stephen R.;Tan, Tricia M. M.;Owen, Bryn M.
• 通讯作者: Owen, Bryn M.