College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University; Bio-MAX Institute, Seoul National University, 29-Room # 311, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Arch Pharm Res. 2021 Feb;44(2):133-145. doi: 10.1007/s12272-021-01314-w. Epub 2021 Feb 7.
The high incidence of obesity has increased the need to discover new therapeutic targets to combat obesity and obesity-related metabolic diseases. Obesity is defined as an abnormal accumulation of adipose tissue, which is one of the major metabolic organs that regulate energy homeostasis. However, there are currently no approved anti-obesity therapeutics that directly target adipose tissue metabolism. With recent advances in the understanding of adipose tissue biology, molecular mechanisms involved in brown adipose tissue expansion and metabolic activation have been investigated as potential therapeutic targets to increase energy expenditure. This review focuses on G-protein coupled receptors (GPCRs) as they are the most successful class of druggable targets in human diseases and have an important role in regulating adipose tissue metabolism. We summarize recent findings on the major GPCR classes that regulate thermogenesis and mitochondrial metabolism in adipose tissue. Improved understanding of GPCR signaling pathways that regulate these processes could facilitate the development of novel pharmacological approaches to treat obesity and related metabolic disorders.
肥胖症的高发率增加了人们对发现新的治疗靶点的需求，以对抗肥胖症和与肥胖相关的代谢性疾病。肥胖症被定义为脂肪组织的异常积累，脂肪组织是调节能量平衡的主要代谢器官之一。然而，目前还没有批准的专门针对脂肪组织代谢的抗肥胖治疗药物。随着人们对脂肪组织生物学理解的不断深入，棕色脂肪组织扩张和代谢激活所涉及的分子机制已被作为增加能量消耗的潜在治疗靶点进行了研究。本篇综述重点介绍了 G 蛋白偶联受体（GPCRs），因为它们是人类疾病中最成功的一类可成药靶点，在调节脂肪组织代谢方面发挥着重要作用。我们总结了近期关于调节脂肪组织产热和线粒体代谢的主要 GPCR 类的发现。更好地了解调节这些过程的 GPCR 信号通路，可能有助于开发治疗肥胖症和相关代谢紊乱的新的药理学方法。
