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Jingxin Liu, Yitao Wang, Ligen Lin. Small molecules for fat combustion: targeting obesity[J]. Acta Pharmaceutica Sinica B, 2019, 9(2): 220-236

Small molecules for fat combustion: targeting obesity
Jingxin Liu, Yitao Wang, Ligen Lin
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa 999078, Macau, China
Abstract:
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 proteincoupled 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.
Key words:    Thermogenesis    Brown adipose tissue    Beige cells    Obesity    Uncoupling protein 1   
Received: 2018-04-27     Revised: 2018-08-01
DOI: 10.1016/j.apsb.2018.09.007
Funds: Financial support by Science and Technology Development Fund,Macao SAR,China (FDCT 102/2017/A) and the Research Fund of University of Macau,China (MYRG2017-00109-ICMS) are gratefully acknowledged.
Corresponding author: Ligen Lin     Email:ligenl@umac.mo
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Jingxin Liu
Yitao Wang
Ligen Lin

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