Increase of Peroxisome Proliferator-activated Receptor δ (PPARδ) by Digoxin to Improve Lipid Metabolism in the Heart of Diabetic Rats

Chen, Z.-C.; Yu, Bu Chin; Chen, L.-J.

doi:10.1055/s-0032-1330021

Cited by 10 publications

(8 citation statements)

References 13 publications

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“…8A). To further explore potential mechanisms underlying this TG accumulation, we assessed the expression of enzymes involved in TG synthesis (GPAT1) or hydrolysis (ATGL and HSL) by immunoblotting, as well as transcript levels of PPARd/b, which has been inversely associated with TG content in diabetic hearts (32). Although GPAT1, ATGL, and HSL immunoreactivity were unchanged, we found significant increases in the phosphorylation of HSL on serine 565 (405%; Fig.…”

Section: Mk2 Deletion Protects Against Diabetes-induced Systemic and mentioning

confidence: 86%

MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction

et al. 2015

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Heart disease remains a major complication of diabetes, and the identification of new therapeutic targets is essential. This study investigates the role of the protein kinase MK2, a p38 mitogen-activated protein kinase downstream target, in the development of diabetes-induced cardiomyopathy. Diabetes was induced in control (MK2(+/+)) and MK2-null (MK2(-/-)) mice using repeated injections of a low dose of streptozotocin (STZ). This protocol generated in MK2(+/+) mice a model of diabetes characterized by a 50% decrease in plasma insulin, hyperglycemia, and insulin resistance (IR), as well as major contractile dysfunction, which was associated with alterations in proteins involved in calcium handling. While MK2(-/-)-STZ mice remained hyperglycemic, they showed improved IR and none of the cardiac functional or molecular alterations. Further analyses highlighted marked lipid perturbations in MK2(+/+)-STZ mice, which encompass increased 1) circulating levels of free fatty acid, ketone bodies, and long-chain acylcarnitines and 2) cardiac triglyceride accumulation and ex vivo palmitate β-oxidation. MK2(-/-)-STZ mice were also protected against all these diabetes-induced lipid alterations. Our results demonstrate the benefits of MK2 deletion on diabetes-induced cardiac molecular and lipid metabolic changes, as well as contractile dysfunction. As a result, MK2 represents a new potential therapeutic target to prevent diabetes-induced cardiac dysfunction.

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Section: Mk2 Deletion Protects Against Diabetes-induced Systemic and mentioning

confidence: 86%

MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction

et al. 2015

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“…Primary cultures of neonatal rat cardiomyocytes were prepared by the modification of a previously described method [18]. Briefly, under anesthesia with 3% isoflurane, the hearts of 1- to 2-day-old Wistar rats were excised, cut into 1–2 mm pieces, and predigested with trypsin to remove red blood cells.…”

Section: Methodsmentioning

confidence: 99%

“…It has been identified that cardiac agent, such as digoxin and dobutamine, can restore the cardiac contractility in diabetic rats [10–12]. Also, cardiac agent improved cardiac contraction in STZ-diabetic rats which is associated with a marked increase in cardiac PPAR δ expression [13].…”

Section: Introductionmentioning

confidence: 99%

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

Lin

Cherng

Chen

et al. 2014

BioMed Research International

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Ginseng has been shown to be effective on cardiac dysfunction. Recent evidence has highlighted the mediation of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Thus, we are interested to investigate the role of PPARδ in ginseng-induced modification of cardiac contractility. The isolated hearts in Langendorff apparatus and hemodynamic analysis in catheterized rats were applied to measure the actions of ginseng ex vivo and in vivo. In normal rats, ginseng enhanced cardiac contractility and hemodynamic dP/dt max significantly. Both actions were diminished by GSK0660 at a dose enough to block PPARδ. However, ginseng failed to modify heart rate at the same dose, although it did produce a mild increase in blood pressure. Data of intracellular calcium level and Western blotting analysis showed that both the PPARδ expression and troponin I phosphorylation were raised by ginseng in neonatal rat cardiomyocyte. Thus, we suggest that ginseng could enhance cardiac contractility through increased PPARδ expression in cardiac cells.

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“…The impaired cardiac PPAR δ expression could be reversed by anti-hypertrophic treatment [34, 36]. Studies using Western blots also showed protein contents of cardiac PPAR δ are downregulated in doxorubicin-cardiac cytotoxicity [37] and STZ-induced diabetic hearts [38]. In contrast to the above investigations, another study using Western blot showed that cardiac PPAR δ is upregulated in the heart with infarction in rats [39].…”

Section: Pparδ Plays a Crucial Role In Cardiac Pathophysiologymentioning

confidence: 99%

“…Diabetes (type 1 and type 2) and obesity have a strong link to cardiac dysfunction, cardiac hypertrophy and heart failure (see review [52–54]). Normalizing cardiac PPAR δ protein improves cardiac fibrosis in rats with streptozocin (STZ)-induced diabetes [37]. Induction of cardiac angiopoietin Like 4 (Angptl4) via PPAR δ activation in the heart is essential in protecting against FA-induced oxidative stress [55], a key mechanism behind diabetic cardiomyopathy.…”

Section: Pparδ Plays a Crucial Role In Cardiac Pathophysiologymentioning

confidence: 99%

PPARδ, a Potential Therapeutic Target for Heart Disease

Yang

Long

2018

Nuclear Receptor Research

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The nuclear receptor peroxisome proliferator-activated receptor δ (PPAR δ ) can transcriptionally regulate target genes. PPAR δ exerts essential regulatory functions in the heart, which requires constant energy supply. PPAR δ plays a key role in energy metabolism, controlling not only fatty acid (FA) and glucose oxidation, but also redox homeostasis, mitochondrial biogenesis, inflammation, and cardiomyocyte proliferation. PPAR δ signaling is impaired in the heart under various pathological conditions, such as pathological cardiac hypertrophy, myocardial ischemia/reperfusion, doxorubicin cardiotoxicity and diabetic cardiomyopathy. PPAR δ deficiency in the heart leads to cardiac dysfunction, myocardial lipid accumulation, cardiac hypertrophy/remodeling and heart failure. This article provides an up-today overview of this research area and discusses the role of PPAR δ in the heart in light of the complex mechanisms of its transcriptional regulation and its potential as a translatable therapeutic target for the treatment of cardiac disorders.

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Increase of Peroxisome Proliferator-activated Receptor δ (PPARδ) by Digoxin to Improve Lipid Metabolism in the Heart of Diabetic Rats

Cited by 10 publications

References 13 publications

MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction

MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

PPARδ, a Potential Therapeutic Target for Heart Disease

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