HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy
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 inhibi...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2016/5938740 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556870348308480 |
|---|---|
| author | Ting-I Lee Yu-Hsun Kao Wen-Chin Tsai Cheng-Chih Chung Yao-Chang Chen Yi-Jen Chen |
| author_facet | Ting-I Lee Yu-Hsun Kao Wen-Chin Tsai Cheng-Chih Chung Yao-Chang Chen Yi-Jen Chen |
| author_sort | Ting-I Lee |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-255604e0763b4223aa46befa23f478cb |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-255604e0763b4223aa46befa23f478cb2025-02-03T05:44:13ZengWileyPPAR Research1687-47571687-47652016-01-01201610.1155/2016/59387405938740HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic CardiomyopathyTing-I Lee0Yu-Hsun Kao1Wen-Chin Tsai2Cheng-Chih Chung3Yao-Chang Chen4Yi-Jen Chen5Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDivision of Cardiology, Tzu-Chi General Hospital, Institute of Medical Sciences, Tzu-Chi University, Hualien 97004, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanDepartment of Biomedical Engineering, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, TaiwanPeroxisome 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.http://dx.doi.org/10.1155/2016/5938740 |
| spellingShingle | Ting-I Lee Yu-Hsun Kao Wen-Chin Tsai Cheng-Chih Chung Yao-Chang Chen Yi-Jen Chen HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy PPAR Research |
| title | HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy |
| title_full | HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy |
| title_fullStr | HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy |
| title_full_unstemmed | HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy |
| title_short | HDAC Inhibition Modulates Cardiac PPARs and Fatty Acid Metabolism in Diabetic Cardiomyopathy |
| title_sort | hdac inhibition modulates cardiac ppars and fatty acid metabolism in diabetic cardiomyopathy |
| url | http://dx.doi.org/10.1155/2016/5938740 |
| work_keys_str_mv | AT tingilee hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy AT yuhsunkao hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy AT wenchintsai hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy AT chengchihchung hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy AT yaochangchen hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy AT yijenchen hdacinhibitionmodulatescardiacpparsandfattyacidmetabolismindiabeticcardiomyopathy |