Wang Yi, Qiu Weiwei, Kernodle Stace, Parker Carly, Padilla Marc-Antonio, Su Jiaao, Tomlinson Abigail J, Oldham Stephanie, Field Joss, Bernard Elise, Hornigold David, Rhodes Christopher J, Olson David P, Seeley Randy J, Myers Martin G
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Mol Metab. 2025 Feb;92:102093. doi: 10.1016/j.molmet.2024.102093. Epub 2025 Jan 2.
Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS cells). Not only does the artificial activation of NTS cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We set out to determine roles for putative PrRP receptors in the response to NTS PrRP and exogenous PrRP-related peptides.
We used animals lacking PrRP receptors GPR10 and/or GPR74 (encoded by Prlhr and Npffr2, respectively) to determine roles for each in the restraint of food intake and body weight by the increased expression of Prlh in NTS neurons (NTS mice) and in response to the anorectic PrRP analog, p52.
Although Prlhr played a crucial role in the restraint of food intake and body weight in HFD-fed control animals, the combined absence of Prlhr and Npffr2 was required to abrogate the restraint of food intake in NTS mice. p52 suppressed feeding independently of both receptors, however.
Hence, each receptor can participate in the NTS-mediated suppression of food intake and body weight gain, while PrRP analog treatment can mediate its effects via distinct systems. While Prlhr plays a crucial role in the physiologic restraint of weight gain, the action of either receptor is capable of ameliorating obesity in response to enhanced NTS signaling.
孤束核（NTS）中的几组神经元可抑制食物摄入，包括表达促泌乳素释放激素（Prlh）的神经元（NTS细胞）。NTS细胞的人工激活不仅会减少进食，而且Prlh（编码神经肽PrRP）的表达以及NTS神经元的神经传递也有助于抑制食物摄入和体重，尤其是在喂食高脂饮食（HFD）的动物中。我们着手确定假定的PrRP受体在对NTS PrRP和外源性PrRP相关肽的反应中的作用。
我们使用缺乏PrRP受体GPR10和/或GPR74（分别由Prlhr和Npffr2编码）的动物，以确定它们各自在通过NTS神经元中Prlh表达增加（NTS小鼠）来抑制食物摄入和体重以及对厌食性PrRP类似物p52的反应中的作用。
尽管Prlhr在喂食HFD的对照动物抑制食物摄入和体重方面起关键作用，但在NTS小鼠中，需要同时缺失Prlhr和Npffr2才能消除对食物摄入的抑制。然而，p52可独立于这两种受体抑制进食。
因此，每种受体都可参与NTS介导的食物摄入和体重增加的抑制，而PrRP类似物治疗可通过不同系统介导其作用。虽然Prlhr在体重增加的生理抑制中起关键作用，但任一受体的作用都能够在NTS信号增强时改善肥胖状况。
