Abstract

Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was downregulated, and the expression of low density lipoprotein receptor (LDLR) was upregulated in sauchinone-treated HepG2 cells. Consequently, LDL-cholesterol (LDL-C) uptake was increased. As a transcriptional regulator of PCSK9 expression, sterol regulatory elements binding protein-2 (SREBP-2) was proposed by transcriptome analysis and western blotting. Oral administration of sauchinone increased hepatic LDLR through PCSK9 inhibition in obese mice and showed the reduced serum LDL-C levels and downstream targets of SREBP-2. Thus, it is evident that sauchinone reduces hepatic steatosis by downregulating the expression of hepatic PCSK9 via SREBP-2.

Details

Title
Sauchinone controls hepatic cholesterol homeostasis by the negative regulation of PCSK9 transcriptional network
Author
Hee-Sung Chae 1 ; You, Byoung Hoon 1 ; Dong-Yeop, Kim 2 ; Lee, Hankyu 1 ; Hyuk Wan Ko 1 ; Hyun-Jeong, Ko 3 ; Choi, Young Hee 1 ; Sun Shim Choi 2 ; Young-Won, Chin 1 

 College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Gyeonggi-do, Republic of Korea 
 Division of Biomedical Convergence, College of Biomedical Science, and Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon, Republic of Korea 
 Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, Republic of Korea 
Pages
1-14
Publication year
2018
Publication date
Apr 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2032768625
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.