title: Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice.
abstract: Tetradecylthioacetic acid (TTA) is a novel peroxisome proliferator-activated receptor (PPAR) ligand with marked hypolipidemic and insulin-sensitizing effects in obese models. TTA has recently been shown to attenuate dyslipidemia in patients with type 2 diabetes, corroborating the potential for TTA in antidiabetic therapy. In a recent study on normal mice, we showed that TTA increased myocardial fatty acid (FA) oxidation, which was associated with decreased cardiac efficiency and impaired postischemic functional recovery. The aim of the present study was, therefore, to elucidate the effects of TTA treatment (0.5%, 8 days) on cardiac metabolism and function in a hyperlipidemic type 2 diabetic model. We found that TTA treatment increased myocardial FA oxidation, not only in nondiabetic (db/+) mice but also in diabetic (db/db) mice, despite a clear lipid-lowering effect. Although TTA had deleterious effects in hearts from nondiabetic mice (decreased efficiency and impaired mitochondrial respiratory capacity), these effects were not observed in db/db hearts. In db/db hearts, TTA improved ischemic tolerance, an effect that is most likely related to the antioxidant property of TTA. The present study strongly advocates the need for investigation of the cardiac effects of PPAR ligands used in antidiabetic/hypolipidemic therapy, because of their pleiotropic properties.
authors.affiliation: Cardiovascular Research Group, Dept. of Medical Biology, Univ. of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Khalid
authors.forename: Anne Dragøy
authors.initials: AD
authors.lastname: Hafstad
authors.forename: Terje S
authors.initials: TS
authors.lastname: Larsen
authors.forename: David L
authors.initials: DL
authors.lastname: Severson
authors.forename: Neoma
authors.initials: N
authors.lastname: Boardman
authors.forename: Martin
authors.initials: M
authors.lastname: Hagve
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Ellen
authors.initials: E
authors.lastname: Aasum
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004579:Electron Transport / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors; D013440:Sulfides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D005227:Fatty Acids; D008024:Ligands; D047492:Peroxisome Proliferator-Activated Receptors; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane