title: Physiological characterization of a novel PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013).
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.
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: An
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.|Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Bonggi
authors.initials: B
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Hyoung Oh
authors.initials: HO
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Seong Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Kyoung Mi
authors.initials: KM
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Ye Ra
authors.initials: YR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Hwi Young
authors.initials: HY
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Inje University, Gyeongsangnam-do 50834, Republic of Korea.
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.affiliation: Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.affiliation: College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.|Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D051381:Rats
chemical_list: D047493:PPAR alpha; D011422:Propionates
keywords: FGF21; MHY2013; PPAR pan agonist; adiponectin; metabolic syndrome