Cardiac metabolism, inflammation, and peroxisome proliferator-activated receptors modulated by 1,25-dihydroxyvitamin D3 in diabetic rats

Background: High free fatty acid with reduced glucose utilization in diabetes mellitus (DM) impairs cardiac function. Peroxisome proliferator-activated receptors (PPARs) modulate myocardial lipid and glucose homeostasis. The active 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) regulates oxidative stress and inflammation, which may play a key role in the modulation of PPARs. The aim of this study was to investigate whether 1,25(OH)(2)D-3 can modulate the cardiac PPARs and fatty acid metabolism. Methods: Electrocardiogram, echocardiogram, and Western blot analysis were used to evaluate cardiac fatty acid metabolism, inflammation, and PPAR isoform expression in Wistar-Kyoto (WKY) rats, DM rats, and DM rats treated with 1,25(OH)(2)D-3. Results: Compared to healthy rats, DM and 1,25(OH)(2)D-3-treated DM rats had lower body weight. DM rats had larger left ventricular end-diastolic diameter, and longer QT interval than healthy or 1,25(OH)(2)D-3-treated DM rats. Moreover, compared to healthy or 1,25(OH)(2)D-3-treated DM rats, DM rats had fewer cardiac PPAR-alpha and PPAR-delta protein expressions, but had increased cardiac PPAR-gamma protein levels, tumor necrosis factor-alpha, interleukin-6, 5 ' adenosine monophosphate-activated protein kinase alpha 2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase 1, PPAR-gamma coactivator 1-alpha, cluster of differentiation 36, and diacylglycerol acyltransferase 2 protein expressions. Conclusions: 1,25(OH)(2)D-3 significantly changed the cardiac function and fatty acid regulations in DM hearts, which may be caused by its regulations on cardiac PPARs and proinflammatory cytokines. (C) 2014 Elsevier Ireland Ltd. All rights reserved.