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

Abstract

// Hye Jin An 1, 2 , Bonggi Lee 1, 2, 5 , Dae Hyun Kim 1, 2 , Eun Kyeong Lee 1, 2 , Ki Wung Chung 1, 2 , Min Hi Park 1, 2 , Hyoung Oh Jeong 1, 2 , Sung Min Kim 1, 2 , Kyoung Mi Moon 1, 2 , Ye Ra Kim 1, 2 , Seong Jin Kim 1, 2 , Hwi Young Yun 1, 2 , Pusoon Chun 3 , Byung Pal Yu 4 , Hyung Ryong Moon 1, 2 , Hae Young Chung 1, 2 1 College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea 2 Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea 3 College of Pharmacy, Inje University, Gyeongsangnam-do 50834, Republic of Korea 4 Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA 5 Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea Correspondence to: Hae Young Chung, email: hyjung@pusan.ac.kr Hyung Ryong Moon, email: mhr108@pusan.ac.kr Keywords: MHY2013, PPAR pan agonist, metabolic syndrome, FGF21, adiponectin Received: July 29, 2016 Accepted: December 27, 2016 Published: January 25, 2017 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.