Quantitative analysis of peroxisome proliferator‐activated receptor gamma (PPARγ) expression in arteries and hearts of patients with ischaemic or dilated cardiomyopathy

Follak

Diabetes Metabolism Res

2004

Section: Discussionmentioning

confidence: 99%

Diabetes per se and metabolic state influence gene expression in tissue‐dependent manner of BB/OK rats

Follak

Diabetes Metabolism Res

2004

“…In contrast, PPARγ is expressed at relatively low levels in the heart [11]–[14] and recent data have shown that tissue specific loss of PPARγ have no effect on expression of gene controlling lipid and glucose metabolism [15]. Furthermore, exposure of myocytes to PPARα or α/γ specific agonists or long-chain fatty acids led to a significant induction of known PPAR target genes involved in fatty acid uptake and oxidation whereas a PPAR agonist had no effect [12].…”

Section: Introductionmentioning

confidence: 99%

Effects of PPARs Agonists on Cardiac Metabolism in Littermate and Cardiomyocyte-Specific PPAR-γ –Knockout (CM-PGKO) Mice

et al. 2012

Understanding the molecular regulatory mechanisms controlling for myocardial lipid metabolism is of critical importance for the development of new therapeutic strategies for heart diseases. The role of PPARγ and thiazolidinediones in regulation of myocardial lipid metabolism is controversial. The aim of our study was to assess the role of PPARγ on myocardial lipid metabolism and function and differentiate local/from systemic actions of PPARs agonists using cardiomyocyte-specific PPARγ –knockout (CM-PGKO) mice. To this aim, the effect of PPARγ, PPARγ/PPARα and PPARα agonists on cardiac function, intra-myocyte lipid accumulation and myocardial expression profile of genes and proteins, affecting lipid oxidation, uptake, synthesis, and storage (CD36, CPT1MIIA, AOX, FAS, SREBP1-c and ADPR) was evaluated in cardiomyocyte-specific PPARγ –knockout (CM-PGKO) and littermate control mice undergoing standard and high fat diet (HFD). At baseline, protein levels and mRNA expression of genes involved in lipid uptake, oxidation, synthesis, and accumulation of CM-PGKO mice were not significantly different from those of their littermate controls. At baseline, no difference in myocardial lipid content was found between CM-PGKO and littermate controls. In standard condition, pioglitazone and rosiglitazone do not affect myocardial metabolism while, fenofibrate treatment significantly increased CD36 and CPT1MIIA gene expression. In both CM-PGKO and control mice submitted to HFD, six weeks of treatment with rosiglitazone, fenofibrate and pioglitazone lowered myocardial lipid accumulation shifting myocardial substrate utilization towards greater contribution of glucose. In conclusion, at baseline, PPARγ does not play a crucial role in regulating cardiac metabolism in mice, probably due to its low myocardial expression. PPARs agonists, indirectly protect myocardium from lipotoxic damage likely reducing fatty acids delivery to the heart through the actions on adipose tissue. Nevertheless a direct non- PPARγ mediated mechanism of PPARγ agonist could not be ruled out.

“…In rodents, TZDs have been shown to cause cardiac hypertrophy during chronic treatment [38]. Interestingly, left ventricular specimens from patients with dilated cardiomyopathy exhibit a significant increase in PPAR-γ expression, whereas the expression of PPAR-γ is nearly undetectable in the healthy heart [39]. These observations have led to speculation that PPAR-γ may be involved in cardiac hypertrophic growth programs or in ventricular remodeling.…”

Section: Role Of Ppar-γmentioning

confidence: 99%

Deranged energy substrate metabolism in the failing heart

Tian¹,

Barger

2006

Current Science Inc

Control of energy metabolism in the heart is closely linked to cardiac performance. Dysregulation of energy-generating pathways occurs in many forms of heart disease, including heart failure. Uncertainty exists as to whether these alterations in the way adenosine triphosphate (ATP) is produced serve to protect the heart from excessive oxygen demands or have untoward long-term consequences. Regulation of fatty acid beta-oxidation (FAO), the principal source of ATP in the healthy heart, occurs at multiple levels, including a strong gene transcriptional component. In the heart, members of the peroxisome proliferator-activated receptor (PPAR) family of transcription factors are the primary regulators of FAO gene expression. PPARs are ligand activated by endogenous lipids and synthetic small molecules, thus providing attractive targets for pharmaceutical intervention. This article discusses controversies surrounding our understanding of cardiac energy metabolism in heart failure and the role that PPAR family members may play, either as contributors to or as potential adjunctive therapy for cardiac disease.