Liu Jingxin, Wang Yitao, Lin Ligen
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa 999078, Macau, China.
Acta Pharm Sin B. 2019 Mar;9(2):220-236. doi: 10.1016/j.apsb.2018.09.007. Epub 2018 Sep 19.
Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches, either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue (BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G protein-coupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous pathways. Advances in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulators might have a large potential for further investigations to be developed as lead compounds in fighting obesity.
肥胖在全球正以惊人的速度增长，这导致了一些疾病的更高风险，如2型糖尿病、心血管疾病和癌症。目前的治疗方法，无论是胰腺脂肪酶抑制剂还是食欲抑制剂，通常效果有限。棕色脂肪组织（BAT）和米色细胞将脂肪酸作为热量散发以维持体温，这被称为非颤抖性产热；BAT和米色细胞的活性和数量与超重和肥胖呈负相关。成年人体内BAT和米色细胞的存在为减肥提供了一种有效的治疗方法，这一过程可能适合进行药物干预。在此，我们梳理了产热的生理学以及BAT和米色细胞在对抗肥胖中的作用。我们总结了过去几十年中确定的产热调节因子，其作用靶点包括G蛋白偶联受体、瞬时受体电位通道、核受体和其他多种途径。还介绍了临床试验的进展。本综述的主要目的是提供全面且最新的知识，涵盖从产热在能量稳态中的生物学重要性到治疗肥胖的代表性产热调节因子。产热调节因子在进一步研究中具有很大潜力，有望开发成为对抗肥胖的先导化合物。
