Centre for Translational Pharmacology, University of Glasgow, Glasgow, United Kingdom.
Front Endocrinol (Lausanne). 2023 Jul 6;14:1197102. doi: 10.3389/fendo.2023.1197102. eCollection 2023.
Metabolic disorders including obesity, diabetes and non-alcoholic steatohepatitis are a group of conditions characterised by chronic low-grade inflammation of metabolic tissues. There is now a growing appreciation that various metabolites released from adipose tissue serve as key signalling mediators, influencing this interaction with inflammation. G protein-coupled receptors (GPCRs) are the largest family of signal transduction proteins and most historically successful drug targets. The signalling pathways for several key adipose metabolites are mediated through GPCRs expressed both on the adipocytes themselves and on infiltrating macrophages. These include three main groups of GPCRs: the FFA4 receptor, which is activated by long chain free fatty acids; the HCA and HCA receptors, activated by hydroxy carboxylic acids; and the succinate receptor. Understanding the roles these metabolites and their receptors play in metabolic-immune interactions is critical to establishing how these GPCRs may be exploited for the treatment of metabolic disorders.
代谢紊乱包括肥胖、糖尿病和非酒精性脂肪性肝炎等疾病，其特征为代谢组织的慢性低度炎症。现在人们越来越认识到，脂肪组织释放的各种代谢物可作为关键的信号转导介质，影响这种与炎症的相互作用。G 蛋白偶联受体（GPCR）是信号转导蛋白中最大的家族，也是历史上最成功的药物靶点。几种关键脂肪代谢物的信号通路是通过在脂肪细胞本身和浸润的巨噬细胞上表达的 GPCR 介导的。这些 GPCR 包括三个主要的受体群：FFA4 受体，其被长链游离脂肪酸激活；HCA 和 HCA 受体，被羟基羧酸激活；以及琥珀酸受体。了解这些代谢物及其受体在代谢-免疫相互作用中的作用对于确定这些 GPCR 如何被用于治疗代谢紊乱至关重要。
