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

Autor:	Dai J; Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China.; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Liang K; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; School of Life Sciences, Peking University, 100871 Beijing, China., Zhao S; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Jia W; State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China.; University of the Chinese Academy of Sciences, 101408 Beijing, China., Liu Y; Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China.; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Wu H; Institute of Molecular Medicine, Peking University, 100871 Beijing, China., Lv J; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; Institute of Molecular Medicine, Peking University, 100871 Beijing, China., Cao C; College of Engineering, Peking University, 100871 Beijing, China., Chen T; College of Engineering, Peking University, 100871 Beijing, China., Zhuang S; Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China.; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Hou X; Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China.; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Zhou S; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Zhang X; College of Engineering, Peking University, 100871 Beijing, China., Chen XW; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; Institute of Molecular Medicine, Peking University, 100871 Beijing, China., Huang Y; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; College of Engineering, Peking University, 100871 Beijing, China., Xiao RP; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; Institute of Molecular Medicine, Peking University, 100871 Beijing, China., Wang YL; State Key Laboratory of Stem Cells and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China., Luo T; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China., Xiao J; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.; School of Life Sciences, Peking University, 100871 Beijing, China., Wang C; Synthetic and Functional Biomolecules Center, Peking University, 100871 Beijing, China; chuwang@pku.edu.cn.; 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.; Peking-Tsinghua Center for Life Sciences, 100871 Beijing, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jun 26; Vol. 115 (26), pp. E5896-E5905. Date of Electronic Publication: 2018 Jun 11.
DOI:	10.1073/pnas.1801745115
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu