MD001, a Novel Peroxisome Proliferator-activated Receptor alpha/gamma Agonist, Improves Glucose and Lipid Metabolism SCIE SCOPUS

Cited 7 time in WEB OF SCIENCE Cited 9 time in Scopus
Title
MD001, a Novel Peroxisome Proliferator-activated Receptor alpha/gamma Agonist, Improves Glucose and Lipid Metabolism
Author(s)
Kim, Seok-Ho; Hong, Shin Hee; Park, Young-Joon; Sung, Jong-Hyuk; Suh, Wonhee; Lee, Kyeong Won; Jung, Kiwon; Lim, Changjin; Kim, Jin-Hee; Kim, Hyoungsu; Park, Kyong Soo; Park, Sang Gyu
KIOST Author(s)
Lee, Kyeong Won(이경원)
Alternative Author(s)
이경원
Publication Year
2019-02-07
Abstract
Peroxisome proliferator-activated receptor (PPAR)-alpha/gamma dual agonists have been developed to treat metabolic diseases; however, most of them exhibit side effects such as body weight gain and oedema. Therefore, we developed a novel PPAR alpha/gamma dual agonist that modulates glucose and lipid metabolism without adverse effects. We synthesised novel compounds composed of coumarine and chalcone, determined their crystal structures, and then examined their binding affinity toward PPAR alpha/gamma. We investigated the expression of PPAR alpha and PPAR gamma target genes by chemicals in HepG2, differentiated 3T3-L1, and C2C12 cells. We examined the effect of chemicals on glucose and lipid metabolism in db/db mice. Only MD001 functions as a PPAR alpha/gamma dual agonist in vitro. MD001 increased the transcriptional activity of PPAR alpha and PPAR gamma, resulting in enhanced expression of genes related to beta-oxidation and fatty acid and glucose uptake. MD001 significantly improved blood metabolic parameters, including triglycerides, free fatty acids, and glucose, in db/db mice. In addition, MD001 ameliorated hepatic steatosis by stimulating beta-oxidation in vitro and in vivo. Our results demonstrated the beneficial effects of the novel compound MD001 on glucose and lipid metabolism as a PPAR alpha/gamma dual agonist. Consequently, MD001 may show potential as a novel drug candidate for the treatment of metabolic disorders.
ISSN
2045-2322
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/679
DOI
10.1038/s41598-018-38281-0
Bibliographic Citation
SCIENTIFIC REPORTS, v.9, 2019
Publisher
NATURE PUBLISHING GROUP
Subject
ARYL METHYL ETHERS; PPAR-ALPHA-AGONIST; INSULIN SENSITIVITY; HEPATIC-DYSFUNCTION; ADIPOSE-TISSUE; HEART-FAILURE; FATTY LIVER; BODY-FAT; DEMETHYLATION; MURAGLITAZAR
Type
Article
Language
English
Document Type
Article
Publisher
NATURE PUBLISHING GROUP
Files in This Item:
There are no files associated with this item.

qrcode

Items in ScienceWatch@KIOST are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse