Peroxisome proliferator-activated receptors (PPARs) control the homeostasis of lipids and glucose in the heart. Inhibitors of the enzyme histone deacetylase (HDAC) have anti-inflammatory properties that may be crucial in controlling PPARs and fatty acid metabolism. This study sought to determine whether the HDAC inhibitor MPT0E014 could influence myocardial PPARs, inflammation, and fatty acid metabolism in DM cardiomyopathy. In order to assess the electrophysiological activity, heart structure, fatty acid metabolism, inflammation, and PPAR isoform expressions in control and streptozotocin-nicotinamide-induced DM rats with or without MPT0E014, electrocardiography, echocardiography, and western blotting were used. DM and MPT0E014-treated DM rats showed decreased body weights and higher blood glucose levels compared to control rats. DM rats had larger left ventricular end-diastolic diameter and longer QT intervals than control and MPT0E014-treated rats did. The cardiac PPAR- and PPAR-protein expressions were higher in the control and MPT0E014-treated DM rats, but the cardiac PPAR- was lower than in the DM rats. The levels of the proteins 5′ adenosine monophosphateactivated protein kinase 2, PPAR-coactivator 1, phosphorylated acetyl CoA carboxylase, cluster of differentiation 36, diacylglycerol acyltransferase 1 (DGAT1), DGAT2, tumour necrosis factor-, and interleukin-6 were also lower in control and MPT0E014-treated DM rats than in By modifying cardiac PPARS, fatty acid metabolism, and proinflammatory cytokines, HDAC inhibition greatly reduced DM cardiomyopathy.
