title: Cardiac metabolism, inflammation, and peroxisome proliferator-activated receptors modulated by 1,25-dihydroxyvitamin D3 in diabetic rats.
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.
authors: 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.
authors: Ting-I
authors: TI
authors: Lee
authors: 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.
authors: Yu-Hsun
authors: YH
authors: Kao
authors: Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan.
authors: Yao-Chang
authors: YC
authors: Chen
authors: Division of Cardiology, Tzu-Chi General Hospital, Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
authors: Wen-Chin
authors: WC
authors: Tsai
authors: 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.
authors: Cheng-Chih
authors: CC
authors: Chung
authors: 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.
authors: Yi-Jen
authors: YJ
authors: Chen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D047492:Peroxisome Proliferator-Activated Receptors; C118756:dihydroxy-vitamin D3; D014807:Vitamin D
keywords: Cardiomyocytes; Diabetes mellitus; Fatty acid metabolism; PPARs; Proinflammatory cytokines; Vitamin D