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Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis [Biochemistry]

Baicalin is a major flavonoid component from the herbal medicine Scutellaria baicalensis that has been shown to have an antisteatosis effect. Through quantitative chemoproteomic profiling, we discovered that baicalin acts as a natural allosteric activator of carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme of fatty acid β-oxidation (FAO). By directly binding to CPT1 and activating its activity to accelerate fatty acid degradation, baicalin can significantly ameliorate symptoms associated with hepatic steatosis and reduce diet-induced obesity (DIO). Our study provides an example of a natural product agonist for CPT1. The results provide mechanistic insights to explain the bioactivity of baicalin in reducing lipid accumulation and introduce exciting opportunities for developing novel flavonoid-based FAO activators for pharmacologically treating DIO and associated metabolic disorders.

Authors:   Jianye Dai; Kai Liang; Shan Zhao; Wentong Jia; Yuan Liu; Hongkun Wu; Jia Lv; Chen Cao; Tao Chen; Shentian Zhuang; Xiaomeng Hou; Shijie Zhou; Xiannian Zhang; Xiao-Wei Chen; Yanyi Huang; Rui-Ping Xiao; Yan-Ling Wang; Tuoping Luo; Junyu Xiao; Chu Wang
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   26
Year:   2018
Pages:   E5896
DOI:   10.1073/pnas.1801745115
Publication date:   26-Jun-2018
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