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• W2897314636 abstract "BackgroundThe pharmacological activation of thermogenesis in brown adipose tissue has long been considered promising strategies to treat obesity. However, identification of safe and effective agents remains a challenge. In this study, we addressed this challenge by developing a cellular system with a fluorescence readout, and applied in a high-throughput manner to screen for FDA-approved drugs that may activate endogenous UCP1 expression in adipocytes.MethodsWe have generated a Ucp1-2A-GFP reporter mouse, in which GFP intensity serves as a surrogate of the endogenous expression level of UCP1 protein; and immortalized brown adipocytes were derived from this mouse model and applied in drug screening. Candidate drugs were further tested in mouse models either fed with normal chow or high fat diet to induce obesity.FindingsBy using the cellular screening platform, we identified a group of FDA-approved drugs that can upregulate UCP1 expression in brown adipocyte, including previously known UCP1 activators and new candidate drugs. Further studies focusing on a previously unreported drug—sutent, revealed that sutent treatment could increase the energy expenditure and inhibit lipid synthesis in mouse adipose and liver tissues, resulting in improved metabolism and resistance to obesity.InterpretationThis study offered an easy-to-use cellular screening system for UCP1 activators, and provided a candidate list of FDA-approved drugs that can potentially treat obesity. Further study of these candidates may shed new light on the drug discovery towards obesity.FundNational Key Research and Development Program and the Strategic Priority Research Program of the Chinese Academy of Sciences, etc. (250 words)." @default.
• W2897314636 created "2018-10-26" @default.
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• W2897314636 date "2018-11-01" @default.
• W2897314636 modified "2023-10-06" @default.
• W2897314636 title "Screening of FDA-approved drugs identifies sutent as a modulator of UCP1 expression in brown adipose tissue" @default.
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• W2897314636 doi "https://doi.org/10.1016/j.ebiom.2018.10.019" @default.
• W2897314636 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6286640" @default.
• W2897314636 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30348622" @default.
• W2897314636 hasPublicationYear "2018" @default.
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