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Scientists Identify Sutent as a Modulator of UCP1 Expression in Brown Ddipose Tissue

Obesity is a major risk factor for the development of the metabolic syndrome, type 2 diabetes, and cardiovascular disease, posing a tremendous burden for patients and the public healthcare system.

Current available drugs to treat obesity mostly center around the reduction of energy-intake, either through appetite-suppressing (e.g., phentermine), or inhibition in intestinal lipid absorption (e.g., orlistat). However, adverse side effects exist with these treatments; alternative strategies, for example, to target energy-expending pathways are therefore demanded, as potential complementary medications to treat obesity.

The discovery of thermogenic brown adipose tissue (BAT) in adult human highlights pharmacological activation of BAT thermogenesis as a potential strategy to promote weight loss. A recent study led by Dr. DING Qiurong from Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences identified a FDA-approved drug sutent that can improve the thermogenic activity of brown adipose tissue and improve metabolism, and thus can be potentially repurposed to treat obesity.

In the study, researchers developed a cellular system with a fluorescence readout that can be applied in a high-throughput manner to identify chemicals that can activate endogenous UCP1 expression in adipocytes, which applies as a surrogate of thermogenic activity in brown adipocytes. Using this system, researchers screened a FDA-approved compound library and identified a group of FDA-approved drugs that can upregulate UCP1 expression in brown adipocytes.

Further in vivo study focusing on the effect of sutent revealed that sutent treatment could increase the energy expenditure and inhibit lipid synthesis in adipose and liver tissues, resulting in improved metabolism and resistance to obesity. This study highlights an easy-to-use cellular screening system for UCP1 activators, and provides a candidate drug that can potentially treat obesity.

Entitled “Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue”, this work has been published online in EBioMedicine on Oct 20th, 2018. This study was funded by grants from Ministry of Science and Technology of PRC, Chinese Academy of Sciences, National Natural Science Foundation of China, etc.

The Schematic Diagram of the Strategy and Discoveries in this Study
(Image by Dr. DING Qiurong's Group)

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Shanghai Institute of Nutrition and Health,
Chinese Academy of Sciences
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