Disease relevance of Ppara

• Peroxisome proliferator-activated receptor-alpha activation reduces salt-dependent hypertension during chronic endothelin B receptor blockade [1].
• Subchronic treatment with OEA reduced body weight gain and triacylglycerol content in liver and adipose tissue of diet-induced obese rats and wild-type mice, but not in obese PPAR-alpha(-/-) mice [2].
• PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP) [3].
• Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in response to starvation, high-fat feeding and hyperthyroidism [4].
• PPAR alpha may play a role in cardiac hypertrophy, but effects on cardiac function, inflammation, and fibrosis are unknown [5].

Psychiatry related information on Ppara

• The effects of OEA on motor activity were similar to those of the TRPV1 agonist capsaicin and were also observed with the peroxisome proliferator-activated receptor-alpha agonist Wy-14643 [6].

High impact information on Ppara

• In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity [7].
• BACKGROUND & AIMS: The peroxisome proliferator-activated nuclear receptors (PPAR-alpha, PPAR-beta, and PPAR-gamma), which modulate the expression of genes involved in energy homeostasis, cell cycle, and immune function, may play a role in hepatic stellate cell activation [8].
• Peroxisome proliferator-activated receptor alpha (PPAR alpha) plays a central role in the cell-specific pleiotropic responses induced by structurally diverse synthetic chemicals designated as peroxisome proliferators [9].
• Here we report the identification of such a transcriptionally active PPAR alpha-interacting cofactor (PRIC) complex from rat liver nuclear extracts that interacts with full-length PPAR alpha in the presence of ciprofibrate, a synthetic ligand, and leukotriene B(4), a natural ligand [9].
• TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-alpha [10].

Chemical compound and disease context of Ppara

• PPAR alpha activator fenofibrate inhibits myocardial inflammation and fibrosis in angiotensin II-infused rats [5].
• CONCLUSIONS: The PPAR-gamma ligand rosiglitazone, but not the PPAR-alpha ligand fenofibrate, decreases intimal hyperplasia following balloon injury in both fatty and lean Zucker rats [11].
• We demonstrate that two distinct ligands of PPAR-alpha (including clofibrate and WY 14643) also cause a substantial reduction of myocardial infarct size in the rat [12].
• However, ethanol inhibited PPAR alpha activation of a reporter gene in H4IIEC3 hepatoma cells expressing alcohol-metabolizing enzymes but not in CV-1 cells, which lack these enzymes [13].
• PPAR alpha/retinoid X receptor extracted from hepatoma cells exposed to ethanol or acetaldehyde bound poorly to an oligonucleotide containing peroxisome proliferator response elements [13].

Biological context of Ppara

• Fructose feeding (10% fructose in drinking water for 2 weeks) induced hepatic lipogenesis and reduced peroxisome proliferator-activated receptor alpha (PPARalpha) expression and fatty acid oxidation [14].
• Additionally, expression of genes-related insulin sensitivity, such as adiponectin receptor 1, was significantly enhanced, and mRNA level of peroxisome proliferator activated receptor-alpha, known as a transcriptional factor related lipid metabolism and insulin signaling in skeletal muscle, was markedly increased in CLA-fed rats [15].
• On the other hand, PPAR alpha-independent mechanisms appear to play a role in controlling apoptosis in the senescent liver [16].
• However, as a heterodimer with retinoid X receptor alpha (RXR alpha), PPAR alpha regulates transcription of genes involved in oxidative stress, cell proliferation and apoptosis [16].
• Increased expression of LFABP by transfection of McA-RH7777 cells increased the secretion of apoB-100, decreased triglyceride biosynthesis and secretion, and increased PPAR alpha mRNA levels [3].

Anatomical context of Ppara

• Real-time reverse transcription-polymerase chain reaction and immunohistochemical analysis demonstrated markedly higher expression of Ppara, Pparg, and Rxra mRNA in labyrinth zone trophoblast as compared with basal zone near term [17].
• Potentiation of tumor necrosis factor alpha-induced secreted phospholipase A2 (sPLA2)-IIA expression in mesangial cells by an autocrine loop involving sPLA2 and peroxisome proliferator-activated receptor alpha activation [18].
• We report the isolation, by RT-PCR, of partial cDNAs encoding the rat peroxisome proliferator-activated receptor (PPAR) isoforms PPAR alpha, PPAR beta, and PPAR gamma and the rat retinoid X receptor (RXR) isoforms RXR alpha, RXR beta, and RXR gamma [19].
• Peroxisome proliferator-activated receptor alpha (PPARalpha) potentiates, whereas PPARgamma attenuates, glucose-stimulated insulin secretion in pancreatic beta-cells [20].
• PPAR gamma mRNA is expressed at low levels in most cell types but is present at levels similar to those of PPAR alpha mRNA in adult astrocytes [19].

Associations of Ppara with chemical compounds

• Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats [14].
• Ciprofibrate and WY-14643 altered the levels of acyl CoA-oxidase mRNA and PPAR alpha mRNA in antrum, but had no effect in corpus [21].
• Clofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist, increases protein expression of cytochrome P450 4A (CYP4A), which is responsible for 20-HETE synthesis in the kidney [1].
• The PPAR alpha agonist fenofibrate had no effect on insulin sensitivity [22].
• In a chronic-dosing study, equiefficacious antihyperglycemic doses of the PPAR gamma agonist pioglitazone and PPAR alpha/gamma dual activator ragaglitazar were administered to obesity-prone male rats [22].

Regulatory relationships of Ppara

• PPAR alpha stimulates the rat gastrin-producing cell [21].
• TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal proteins in rat liver [23].
• The peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist Wy-14643 stimulated UCP-2 mRNA levels as effectively as EPA [24].
• The peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear receptor super-family of ligand-activated transcription factors and it functions as an obligate heterodimer with retinoid X-receptor alpha RXRalpha [25].
• p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor alpha: a potential role in the cardiac metabolic stress response [26].

Other interactions of Ppara

• Together, these data indicate that sPLA2-IIA released from mesangial cells by TNF alpha stimulates its own expression via an autocrine loop involving cPLA2 and PPAR alpha [18].
• There was also a marked increase in Pparg (65%, P < 0.05) and Ppara (91%, P < 0.05) mRNA specifically in the labyrinth zone over the final third of pregnancy [17].
• Results from this study suggest that alterations in peroxisomal metabolism observed in the senescent liver may be a result of the decline in the availability of RXR alpha receptor, and not the primary PPAR alpha receptor [16].
• Therefore, chronic PPAR-alpha agonist treatment reduces salt-dependent hypertension produced by ETB receptor blockade in male and female Sprague-Dawley rats [1].
• Effect of PPAR-alpha and -gamma agonist on the expression of visfatin, adiponectin, and TNF-alpha in visceral fat of OLETF rats [27].

Analytical, diagnostic and therapeutic context of Ppara

• To see whether the effects of ciprofibrate could be imitated, rats were given another PPAR alpha ligand WY-14643 or the PPAR gamma ligand troglitazone by gastric intubations daily for 28 and 56 days [21].
• We present the expression patterns of the PPAR subtypes in the adult rat, determined by in situ hybridization using specific probes for PPAR-alpha, -beta and -gamma, and by immunohistochemistry using a polyclonal antibody that recognizes the three rat PPAR subtypes [28].
• We isolated a naturally occurring variant form of PPAR alpha (hPPAR alpha-6/29) from human liver by PCR cloning. hPPAR alpha-6/29 shared the ability of mPPAR alpha to bind to DNA but, unlike mPPAR alpha, could not be activated by PPs [29].
• RT-PCR and ELISA were used to measure TNFalpha, PPAR alpha, and PPAR gamma expression in cultured cardiac myocytes [30].
• Immunoprecipitation of endogenous PPAR alpha from primary rat adipocytes prelabeled with [32P]-orthophosphate and pretreated for 2 h with vanadate and okadaic acid demonstrated for the first time that PPAR alpha is a phosphoprotein in vivo [31].

References