Activation of Receptors δ (PPARδ) by Agonist (GW0742) may Enhance Lipid Metabolism in Heart both In Vivo and In Vitro

Kuo, Shu‐Chun; Ku, Po-Ming; Chen, L.-J.; Niu, Ho‐Shan

doi:10.1055/s-0033-1348317

Cited by 13 publications

(13 citation statements)

References 15 publications

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“…Moreover, while TG accumulation occurs without changes in the abundance of enzymes involved in TG synthesis (DGAT1) or hydrolysis (HSL and ATGL), there was, however, increased AMPKdependent phosphorylation of HSL, which is known to inhibit its activity and is consistent with increased TG accumulation (33). These changes were also consistent with a decrease in PPARb/d expression, which was previously shown to parallel cardiac TG accumulation (44). The fact that the MVO 2 tended to be slightly decreased in diabetic MK2 +/+ hearts suggests, however, that globally mitochondrial oxidative metabolism, which encompasses absolute b-oxidation flux rate from FAs, both exogenously supplied and endogenously formed from TG, would also be decreased.…”

Section: Discussionsupporting

confidence: 85%

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: Discussionsupporting

confidence: 85%

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

et al. 2015

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“…Also, it has been documented that ginseng increases cardiac lipid metabolism by enhancement of PPAR δ expression and this action of ginseng can be blocked by the specific antagonist GSK0660 [44]. In this study, we found that ginseng could increase PPAR δ expression and TnI phosphorylation in the heart of diabetic rats.…”

Section: Discussionsupporting

confidence: 61%

Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Tsai

Chan

Chen

et al. 2014

BioMed Research International

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The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ). We used streptozotocin-induced diabetic rat (STZ-rat) to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats) received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats.

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“…Also, it has been documented that ginseng increases cardiac lipid metabolism by enhancement of PPAR δ expression in the hearing [27]. In this study, we found that ginseng could increase PPAR δ expression and TnI phosphorylation.…”

Section: Discussionsupporting

confidence: 63%

“…Furthermore, activation of PPAR δ using ginseng enhanced cardiac contractility in the isolated hearts and the hemodynamic dP / dt max⁡ in the rats. Both actions of ginseng were inhibited by GSK0660 at a concentration sufficient to block PPAR δ [27, 28]. The enhancement of cardiac contractility by ginseng through an activation of PPAR δ is then characterized.…”

Section: Discussionmentioning

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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Activation of Receptors δ (PPARδ) by Agonist (GW0742) may Enhance Lipid Metabolism in Heart both In Vivo and In Vitro

Cited by 13 publications

References 15 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

Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

Ginseng Is Useful to Enhance Cardiac Contractility in Animals

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