TY - JOUR
T1 - Cardiac metabolism, inflammation, and peroxisome proliferator-activated receptors modulated by 1,25-dihydroxyvitamin D3 in diabetic rats
AU - Lee, Ting I.
AU - Kao, Yu Hsun
AU - Chen, Yao Chang
AU - Tsai, Wen Chin
AU - Chung, Cheng Chih
AU - Chen, Yi Jen
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
KW - Cardiomyocytes
KW - Diabetes mellitus
KW - Fatty acid metabolism
KW - PPARs
KW - Proinflammatory cytokines
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=84906318851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906318851&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2014.07.021
DO - 10.1016/j.ijcard.2014.07.021
M3 - Article
C2 - 25062566
AN - SCOPUS:84906318851
SN - 0167-5273
VL - 176
SP - 151
EP - 157
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 1
ER -