Devère Mélodie, Takhlidjt Saloua, Prévost Gaëtan, Chartrel Nicolas, Leprince Jérôme, Picot Marie
University Rouen Normandie, Inserm, NorDiC UMR 1239, Normandie University, Rouen, France.
Department of Endocrinology, Diabetes and Metabolic Diseases, University Rouen Normandie, Inserm, Normandie University, NorDiC UMR 1239, CHU Rouen, Rouen, France.
Neuroendocrinology. 2025;115(2):111-127. doi: 10.1159/000538629. Epub 2024 Apr 10.
Obesity and type 2 diabetes are strongly associated pathologies, currently considered as a worldwide epidemic problem. Understanding the mechanisms that drive the development of these diseases would enable to develop new therapeutic strategies for their prevention and treatment. Particularly, the role of the brain in energy and glucose homeostasis has been studied for 2 decades. In specific, the hypothalamus contains well-identified neural networks that regulate appetite and potentially also glucose homeostasis. A new concept has thus emerged, suggesting that obesity and diabetes could be due to a dysfunction of the same, still poorly understood, neural networks.
The neuropeptide 26RFa (also termed QRFP) belongs to the family of RFamide regulatory peptides and has been identified as the endogenous ligand of the human G protein-coupled receptor GPR103 (QRFPR). The primary structure of 26RFa is strongly conserved during vertebrate evolution, suggesting its crucial roles in the control of vital functions. Indeed, the 26RFa/GPR103 peptidergic system is reported to be involved in the control of various neuroendocrine functions, notably the control of energy metabolism in which it plays an important role, both centrally and peripherally, since 26RFa regulates feeding behavior, thermogenesis and lipogenesis. Moreover, 26RFa is reported to control glucose homeostasis both peripherally, where it acts as an incretin, and centrally, where the 26RFa/GPR103 system relays insulin signaling in the brain to control glucose metabolism.
This review gives a comprehensive overview of the role of the 26RFa/GPR103 system as a key player in the control of energy and glucose metabolism. In a pathophysiological context, this neuropeptidergic system represents a prime therapeutic target whose mechanisms are highly relevant to decipher.
肥胖症与2型糖尿病是密切相关的病症，目前被视为全球性的流行问题。了解驱动这些疾病发展的机制将有助于开发预防和治疗它们的新策略。特别是，大脑在能量和葡萄糖稳态中的作用已经研究了20年。具体而言，下丘脑包含明确的神经网络，可调节食欲，也可能调节葡萄糖稳态。因此出现了一个新的概念，即肥胖症和糖尿病可能是由于同一神经网络功能失调所致，而该神经网络仍未得到充分了解。
神经肽26RFa（也称为QRFP）属于RF酰胺调节肽家族，已被确定为人类G蛋白偶联受体GPR103（QRFPR）的内源性配体。26RFa的一级结构在脊椎动物进化过程中高度保守，表明其在控制重要功能方面发挥着关键作用。事实上，据报道26RFa/GPR103肽能系统参与多种神经内分泌功能的控制，特别是能量代谢的控制，它在中枢和外周都发挥着重要作用，因为26RFa调节进食行为、产热和脂肪生成。此外，据报道26RFa在外周作为肠促胰岛素控制葡萄糖稳态，在中枢，26RFa/GPR103系统传递大脑中的胰岛素信号以控制葡萄糖代谢。
本综述全面概述了26RFa/GPR103系统在控制能量和葡萄糖代谢中作为关键参与者的作用。在病理生理背景下，这种神经肽能系统是一个主要的治疗靶点，其机制与解密高度相关。
