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  3. Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis

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

  • Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E5896-E5905. doi: 10.1073/pnas.1801745115.
Jianye Dai 1 2 3,  Kai Liang 3 4,  Shan Zhao 2 3,  Wentong Jia 5 6,  Yuan Liu 1 2 3,  Hongkun Wu 7,  Jia Lv 3 7,  Chen Cao 8,  Tao Chen 8,  Shentian Zhuang 1 2 3,  Xiaomeng Hou 1 2 3,  Shijie Zhou 2 3,  Xiannian Zhang 8,  Xiao-Wei Chen 3 7,  Yanyi Huang 3 8,  Rui-Ping Xiao 3 7,  Yan-Ling Wang 5,  Tuoping Luo 2 3,  Junyu Xiao 3 4,  Chu Wang 9 2 3
Affiliations

Affiliations

  • 1 Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China.
  • 2 Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China.
  • 3 Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.
  • 4 School of Life Sciences, Peking University, 100871 Beijing, China.
  • 5 State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.
  • 6 University of the Chinese Academy of Sciences, 101408 Beijing, China.
  • 7 Institute of Molecular Medicine, Peking University, 100871 Beijing, China.
  • 8 College of Engineering, Peking University, 100871 Beijing, China.
  • 9 Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China; [email protected].
PMID: 29891721 DOI: 10.1073/pnas.1801745115
Abstract

Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling Enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.

Keywords

CPT1; baicalin; chemical proteomics; obesity; steatosis.

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