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

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

  • Sci Rep. 2019 Feb 7;9(1):1656. doi: 10.1038/s41598-018-38281-0.
Seok-Ho Kim 1,  Shin Hee Hong 2,  Young-Joon Park 2,  Jong-Hyuk Sung 3,  Wonhee Suh 4,  Kyeong Won Lee 5,  Kiwon Jung 1,  Changjin Lim 1,  Jin-Hee Kim 3,  Hyoungsu Kim 2,  Kyong Soo Park 6,  Sang Gyu Park 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Pocheon, Gyeonggi-do, 11160, Korea.
  • 2 College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, 16499, Korea.
  • 3 College of Pharmacy, Yonsei University, Songdo, Incheon, 405-750, Korea.
  • 4 College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea.
  • 5 Marine Biotechnology Research Center, Korea Institute of Ocean Science & Technology 787 Haeanlo, Ansan, Gyeonggi-do, 426-744, Korea.
  • 6 The Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea.
  • 7 College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, 16499, Korea. sgpark@ajou.ac.kr.
PMID: 30733541 DOI: 10.1038/s41598-018-38281-0
Abstract

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 expression of PPARα and PPARγ 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 PPARα/γ dual agonist in vitro. MD001 increased the transcriptional activity of PPARα and PPARγ, resulting in enhanced expression of genes related to β-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 β-oxidation in vitro and in vivo. Our results demonstrated the beneficial effects of the novel compound MD001 on glucose and lipid metabolism as a PPARα/γ dual agonist. Consequently, MD001 may show potential as a novel drug candidate for the treatment of metabolic disorders.

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