HDAC inhibition modulates cardiac PPARs and fatty acid metabolism in diabetic cardiomyopathy

Ting I. Lee, Yu Hsun Kao, Wen Chin Tsai, Cheng Chih Chung, Yao Chang Chen, Yi Jen Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptors (PPARs) regulate cardiac glucose and lipid homeostasis. Histone deacetylase (HDAC) inhibitor has anti-inflammatory effects which may play a key role in modulating PPARs and fatty acid metabolism. The aim of this study was to investigate whether HDAC inhibitor, MPT0E014, can modulate myocardial PPARs, inflammation, and fatty acid metabolism in diabetes mellitus (DM) cardiomyopathy. Electrocardiography, echocardiography, and western blotting were used to evaluate the electrophysiological activity, cardiac structure, fatty acid metabolism, inflammation, and PPAR isoform expressions in the control and streptozotocin-nicotinamide-induced DM rats with or without MPT0E014. Compared to control, DM and MPT0E014-treated DM rats had elevated blood glucose levels and lower body weights. However, MPT0E014-treated DM and control rats had smaller left ventricular end-diastolic diameter and shorter QT interval than DM rats. The control and MPT0E014-treated DM rats had greater cardiac PPAR-α and PPAR-δ protein expressions, but less cardiac PPAR-γ than DM rats. Moreover, control and MPT0E014-treated DM rats had lower concentrations of 5′ adenosine monophosphate-activated protein kinase 2α, PPAR-γ coactivator 1α, phosphorylated acetyl CoA carboxylase, cluster of differentiation 36, diacylglycerol acyltransferase 1 (DGAT1), DGAT2, tumor necrosis factor-α, and interleukin-6 protein than DM rats. HDAC inhibition significantly attenuated DM cardiomyopathy through modulation of cardiac PPARS, fatty acid metabolism, and proinflammatory cytokines.

Original languageEnglish
Article number5938740
JournalPPAR Research
Volume2016
DOIs
Publication statusPublished - 2016

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Diabetic Cardiomyopathies
Peroxisome Proliferator-Activated Receptors
Histone Deacetylases
Diabetes Mellitus
Fatty Acids
Histone Deacetylase Inhibitors
Cardiomyopathies
Diacylglycerol O-Acyltransferase
Inflammation
Acetyl-CoA Carboxylase
Niacinamide
Adenosine Monophosphate
Streptozocin
Protein Kinases
Echocardiography
Blood Glucose
3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide
Interleukin-6
Electrocardiography
Protein Isoforms

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Drug Discovery

Cite this

HDAC inhibition modulates cardiac PPARs and fatty acid metabolism in diabetic cardiomyopathy. / Lee, Ting I.; Kao, Yu Hsun; Tsai, Wen Chin; Chung, Cheng Chih; Chen, Yao Chang; Chen, Yi Jen.

In: PPAR Research, Vol. 2016, 5938740, 2016.

Research output: Contribution to journalArticle

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