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 D₃ (1,25(OH)₂D 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)₂D₃ 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)₂D₃. Results Compared to healthy rats, DM and 1,25(OH)₂D₃-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)₂D₃-treated DM rats. Moreover, compared to healthy or 1,25(OH)₂D₃-treated DM rats, DM rats had fewer cardiac PPAR-α and PPAR-δ protein expressions, but had increased cardiac PPAR-γ protein levels, tumor necrosis factor-α, interleukin-6, 5′ adenosine monophosphate- activated protein kinaseα2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase 1, PPAR-γ coactivator 1-α, cluster of differentiation 36, and diacylglycerol acyltransferase 2 protein expressions. Conclusions 1,25(OH)₂D₃ 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.