Physiological characterization of a novel PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)- 2-methylpropanoic acid (MHY2013)

11Citations
Citations of this article
15Readers
Mendeley users who have this article in their library.

Abstract

Recently, agonists targeting multiple peroxisome proliferator-activated receptors (PPARs) have been developed to improve metabolic disorders and minimize the side effects of selective PPAR agonists such as weight gain and dyslipidemia. We newly synthesized six 2-methyl-2-(o-tolyloxy)propanoic acid derivatives based on the structure of a well-known PPAR pan agonist, bezafibrate. Of six compounds, MHY2013 was screened as the strongest activator of three PPAR subtypes based on protein docking simulation and luciferase assays. When treated orally in db/db mice, MHY2013 ameliorated obesity-induced insulin resistance, dyslipidemia, and hepatic steatosis without changes of the body weight and levels of liver and kidney injury markers. MHY2013 decreased the serum triglyceride and fatty acid levels, which is associated with an increase in fatty acid oxidation signaling in the liver and thermogenic signaling on white adipose tissue, respectively. Furthermore, MHY2013 markedly increased serum levels of insulin-sensitizing hormones including fibroblast growth factor 21 (FGF21) and adiponectin. In conclusion, this study suggests that, MHY2013 is a novel PPAR pan agonist that improves obesity-induced insulin resistance, dyslipidemia and hepatic steatosis and elevates insulin-sensitizing hormones in the blood.

Cite

CITATION STYLE

APA

An, H. J., Lee, B., Kim, D. H., Lee, E. K., Chung, K. W., Park, M. H., … Chung, H. Y. (2017). Physiological characterization of a novel PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)- 2-methylpropanoic acid (MHY2013). Oncotarget, 8(10), 16912–16924. https://doi.org/10.18632/oncotarget.14818

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free