Khalid 2011 Am J Physiol Heart Circ Physiol

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Khalid AM, Hafstad AD, Larsen TS, Severson DL, Boardman N, Hagve M, Berge RK, Aasum E (2011) Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice. Am J Physiol Heart Circ Physiol 300:H2116-22.

» PMID: 21421822 Open Access

Khalid AM, Hafstad AD, Larsen TS, Severson DL, Boardman N, Hagve M, Berge RK, Asum E (2011) Am J Physiol Heart Circ Physiol

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. Keywords: Diabetic cardiomyopathy, Cardiac metabolism, Ischemia-reperfusion, Cardiac function, Cardiac efficiency

O2k-Network Lab: NO Tromsoe Larsen TS, NO Bergen Berge RK

Labels: Pathology: Diabetes  Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 

HRR: Oxygraph-2k