Dataset Information

MD001, a Novel Peroxisome Proliferator-activated Receptor ?/? Agonist, Improves Glucose and Lipid Metabolism.

ABSTRACT: Peroxisome proliferator-activated receptor (PPAR)-?/? 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?/? 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?/?. We investigated the expression of PPAR? and PPAR? 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?/? dual agonist in vitro. MD001 increased the transcriptional activity of PPAR? and PPAR?, resulting in enhanced expression of genes related to ?-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 ?-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?/? dual agonist. Consequently, MD001 may show potential as a novel drug candidate for the treatment of metabolic disorders.

SUBMITTER: Kim SH

PROVIDER: S-EPMC6367362 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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MD001, a Novel Peroxisome Proliferator-activated Receptor α/γ Agonist, Improves Glucose and Lipid Metabolism.

Kim Seok-Ho SH Hong Shin Hee SH Park Young-Joon YJ Sung Jong-Hyuk JH Suh Wonhee W Lee Kyeong Won KW Jung Kiwon K Lim Changjin C Kim Jin-Hee JH Kim Hyoungsu H Park Kyong Soo KS Park Sang Gyu SG

Scientific reports 20190207 1

Peroxisome proliferator-activated receptor (PPAR)-α/γ 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 PPARα/γ 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 PPARα/γ. We investigated the ...[more]

PMID: 30733541

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Dataset Information

MD001, a Novel Peroxisome Proliferator-activated Receptor ?/? Agonist, Improves Glucose and Lipid Metabolism.

Publications

MD001, a Novel Peroxisome Proliferator-activated Receptor α/γ Agonist, Improves Glucose and Lipid Metabolism.

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