Chaves-Almagro C, Castan-Laurell I, Dray C, Knauf C, Valet P, Masri B
Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
Eur J Pharmacol. 2015 Sep 15;763(Pt B):149-59. doi: 10.1016/j.ejphar.2015.05.017. Epub 2015 May 22.
The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis and energy metabolism regulation. On the other hand, this couple ligand-receptor is also involved in the development and progression of different pathologies including diabetes, obesity, cardiovascular disease and cancer. Recently, a new endogenous peptidic ligand of APJ, named Elabela/Toddler, has been identified and shown to play a crucial role in embryonic development. Whereas nothing is yet known regarding Elabela/Toddler functions in adulthood, apelin has been extensively described as a beneficial adipokine regarding to glucose and lipid metabolism and is endowed with anti-diabetic and anti-obesity properties. Indeed, there is a growing body of evidence supporting apelin signaling as a novel promising therapeutic target for metabolic disorders (obesity, type 2 diabetes). In this review, we provide an overview of the pharmacological properties of APJ and its endogenous ligands. We also report the activity of peptidic and non-peptidic agonists and antagonists targeting APJ described in the literature. Finally, we highlight the important role of this signaling pathway in the control of energy metabolism at the peripheral level and in the central nervous system in both physiological conditions and during obesity or diabetes.
G蛋白偶联受体APJ及其同源配体apelin在人体中广泛表达。它们参与不同的关键生理过程，如血管生成、心血管功能、液体稳态和能量代谢调节。另一方面，这种配体-受体对也参与了包括糖尿病、肥胖症、心血管疾病和癌症在内的不同疾病的发生和发展。最近，一种名为Elabela/Toddler的APJ新内源性肽配体已被鉴定出来，并显示在胚胎发育中起关键作用。虽然目前对Elabela/Toddler在成年期的功能尚不清楚，但apelin已被广泛描述为一种对葡萄糖和脂质代谢有益的脂肪因子，并具有抗糖尿病和抗肥胖特性。事实上，越来越多的证据支持apelin信号通路作为代谢紊乱（肥胖症、2型糖尿病）一种新的有前景的治疗靶点。在这篇综述中，我们概述了APJ及其内源性配体的药理学特性。我们还报告了文献中描述的靶向APJ的肽类和非肽类激动剂及拮抗剂的活性。最后，我们强调了这一信号通路在生理条件下以及肥胖或糖尿病期间对外周水平和中枢神经系统能量代谢控制中的重要作用。
