Key result
Oral administration of the PPARalpha ligand BM 17.0744 to diabetic mice normalized cardiac metabolism but did not improve cardiac contractile function.
Why the study?
Does BM 17.0744 improve cardiac metabolism and contractile function in control and type 2 diabetic (db/db) mice?
Does BM 17.0744 improve cardiac metabolism and contractile function in control and type 2 diabetic (db/db) mice?
Chronic administration of the PPARalpha ligand BM 17.0744 normalized cardiac metabolism in diabetic mice likely via systemic glucose lowering, but failed to improve cardiac contractile function.
Challenges metabolic correction as sufficient for contractile recovery in diabetic cardiomyopathy; leaves open PPARalpha ligand utility in translational research.
Peroxisome proliferator-activated receptor-alpha (PPARalpha) regulates the expression of fatty acid (FA) oxidation genes in liver and heart. Although PPARalpha ligands increased FA oxidation in cultured cardiomyocytes, the cardiac effects of chronic PPARalpha ligand administration in vivo have not been studied. Diabetic db/db mouse hearts exhibit characteristics of a diabetic cardiomyopathy, with altered metabolism and reduced contractile function. A testable hypothesis is that chronic administration of a PPARalpha agonist to db/db mice will normalize cardiac metabolism and improve contractile function. Therefore, a PPARalpha ligand (BM 17.0744) was administered orally to control and type 2 diabetic (db/db) mice (37.9 +/- 2.5 mg/(kg.d) for 8 weeks), and effects on cardiac metabolism and contractile function were assessed. BM 17.0744 reduced plasma glucose in db/db mice, but no change was observed in control mice. FA oxidation was significantly reduced in BM 17.0744 treated db/db hearts with a corresponding increase in glycolysis and glucose oxidation; glucose and FA oxidation in control hearts was unchanged by BM 17.0744. PPARalpha treatment did not alter expression of PPARalpha target genes in either control or diabetic hearts. Therefore, metabolic alterations in hearts from PPARalpha-treated diabetic mice most likely reflect indirect mechanisms related to improvement in diabetic status in vivo. Despite normalization of cardiac metabolism, PPARalpha treatment did not improve cardiac function in diabetic hearts.
No takes yet. Share an insight, caveat, or question.
Aasum et al. (2005) studied Type 2 diabetes. BM 17.0744 vs. Control mice was evaluated on Cardiac metabolism and contractile function. Oral administration of the PPARalpha ligand BM 17.0744 to diabetic mice normalized cardiac metabolism but did not improve cardiac contractile function.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: