Ting-I Lee1, Yu-Hsun Kao2, Yao-Chang Chen3, Wen-Chin Tsai4, Cheng-Chih Chung5, Yi-Jen Chen6. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 2. Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: yuhsunkao@gmail.com. 3. Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan. 4. Division of Cardiology, Tzu-Chi General Hospital, Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan. 5. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 6. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: a9900112@ms15.hinet.net.
Abstract
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)2D3) 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.
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)2D3) 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, DMrats, and DMrats treated with 1,25(OH)2D3. RESULTS: Compared to healthy rats, DM and 1,25(OH)2D3-treated DMrats had lower body weight. DMrats had larger left ventricular end-diastolic diameter, and longer QT interval than healthy or 1,25(OH)2D3-treated DMrats. Moreover, compared to healthy or 1,25(OH)2D3-treated DMrats, DMrats 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.