Disease relevance of PPARD

• PPARD and PPARG haplotypes are independent determinants of plasma levels of lipids, severity of coronary atherosclerosis and its response to therapy [1].
• This association was not observed in a Korean population in a separate study, but this study showed a link between the PPARD polymorphism and body weight and fasting plasma glucose [2].
• Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands [3].
• Recently, it has been shown that PPAR-delta serves as a widespread regulator of fat burning, suggesting that it might be a potential target in the treatment of obesity and type 2 diabetes [4].
• The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases [4].

Psychiatry related information on PPARD

• PPARD haplotype influences cholesterol metabolism but is no risk factor of Alzheimer's disease [5].
• This study demonstrates the effectiveness of a modified Double ABCX or FAAR model in predicting successful adaptation--good marital adjustment, few maternal depressive symptoms, and an in-home rating of family functioning--in 45 families of autistic and communication-impaired children [6].

High impact information on PPARD

• PPARB was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells [7].
• The three 'lipid-sensing' peroxisome proliferator-activated receptors (PPAR-alpha, PPAR-gamma and PPAR-delta) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bona fide therapeutic targets [8].
• Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth [9].
• The most prominent effect was on polyp size; mice treated with the PPAR-delta activator had a fivefold increase in the number of polyps larger than 2 mm [9].
• We treated Apc(min) mice, which are predisposed to intestinal polyposis, with a selective synthetic agonist of peroxisome proliferator-activated receptor-delta (PPAR-delta) [9].

Chemical compound and disease context of PPARD

• OBJECTIVES: The purpose of this pilot study is to explore the clinical efficacy of the topical application of potent PPARbeta/delta and gamma agonists on plaque psoriasis, tetradecylthioacetic acid (TTA) and rosiglitazone, respectively [10].
• Peroxisome proliferators-activated receptor alpha, PPARbeta, PPARgamma1, and PPARgamma2 mRNA are all present in normal peritoneal and adhesion fibroblasts, and selectively rose in response to hypoxia and either DCA or NS-398 [11].
• Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer [12].
• Docosahexaenoic acid membrane content and mRNA expression of acyl-CoA oxidase and of peroxisome proliferator-activated receptor-delta are modulated in Y79 retinoblastoma cells differently by low and high doses of alpha-linolenic acid [13].

Biological context of PPARD

• In the placebo group, subjects possessing both the 482Ser allele of the PPAR-gamma coactivator-1alpha gene (PGC-1A) and the rare allele of two SNPs of PPARD (rs6902123 and rs3734254) had up to 2.5-fold increased risk for diabetes [14].
• Furthermore, women carrying the C allele of rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-gamma2 gene (PPARG2) had a 3.9-fold (95% CI 1.79-8.63; P = 0.001)-higher risk for diabetes than women with protective genotypes [14].
• The baseline plasma triglyceride levels and their responses to treatment with fluvastatin were associated with PPARD haplotypes (P = 0.01) [1].
• We investigated the association between the polymorphism (-87T/C) of the human PPARD gene and phenotypes related to body weight, insulin sensitivity, glucose and lipid metabolism in Chinese subjects [2].
• Aims Previous studies have shown that the peroxisome proliferator-activated receptor delta (PPARD) genetic polymorphism affects cholesterol metabolism in Whites [2].

Anatomical context of PPARD

• Our results also underline the importance of PTGIS and PPARD in the trophoblast and PTGIR in the uterus, suggesting that PGI2 is of both uterine and trophoblastic origin and is involved in a complex signalling pathway at around the time of implantation in the ewe [15].
• The human peroxisome proliferator-activated receptor (PPAR) subtype NUC1 represses the activation of hPPAR alpha and thyroid hormone receptors [16].
• The peroxisome proliferator-activated receptor delta promotes lipid accumulation in human macrophages [17].
• We report that THP-1 monocytes express predominantly PPAR gamma isoform and lower levels of PPAR alpha and PPAR delta isoforms [18].
• Furthermore, PPAR delta appeared to be important for adaptive response of skeletal muscle to environmental changes, such as physical exercise [19].

Associations of PPARD with chemical compounds

• Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial [14].
• CONCLUSIONS: PPARD plays a role in cholesterol metabolism in man [20].
• The PPARD gene is located at 14 cR from the colipase gene and 15 cR from the serine kinase gene at chromosomal region 6p21.2 [21].
• Repression is specific since hNUC1 does not significantly repress activation by the progesterone or retinoic acid receptors [16].
• Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives [22].

Physical interactions of PPARD

• PPRE-1, at-323 bases relative to the start site, is not required for the induction of SSAT by sulindac sulfone but can be bound by both PPAR delta and PPAR gamma [23].

Regulatory relationships of PPARD

• We propose that hNUC1 represses the activity of hPPAR alpha by titrating out a factor required for activation [16].
• PPAR-beta/delta (PPAR-b/d) overexpression suppresses the activity of PPAR-gamma (PPAR-g) and PPAR-alpha [24].
• Here, we report that intracellular prostacyclin formed by expressing prostacyclin synthase in human embryonic kidney 293 cells promotes apoptosis by activating endogenous peroxisome proliferator-activated receptor delta (PPAR delta) [25].
• Taken together, these findings suggest that activation of PPARbeta/delta induces PGE2 receptor subtype EP4 expression through PI3-K signals and increases human lung carcinoma cell proliferation in response to PGE2 [26].
• Waterborne gemfibrozil challenges the hepatic antioxidant defense system and down-regulates peroxisome proliferator-activated receptor beta (PPARbeta) mRNA levels in male goldfish (Carassius auratus) [27].

Other interactions of PPARD

• Its expression is increased by PPARalpha, beta, and gamma in RT4 cells and only by PPARbeta in T24 cells via a transcriptional activation of the VEGF promoter through an indirect mechanism [28].
• PPARs consist of three families, PPAR-alpha, PPAR-delta and PPAR-gamma [29].
• The PPARD and PPARG SNPs were in LD [1].
• Cross-talk between peroxisome proliferator-activated receptor delta and cytosolic phospholipase A(2)alpha/cyclooxygenase-2/prostaglandin E(2) signaling pathways in human hepatocellular carcinoma cells [30].
• Peroxisome proliferator-activated receptor (PPAR)alpha and PPARdelta (also known as PPARbeta) mediate human UCP3 gene regulation by fatty acids through a direct-repeat (DR-1) element in the promoter [31].

Analytical, diagnostic and therapeutic context of PPARD

• In addition, the chromosomal sublocalization of PPARD was determined by radiation hybrid mapping [21].
• RESULTS: PPAR alpha, PPAR beta and PPAR gamma mRNA were detected by using RT-PCR in HUVECs [32].
• We investigated the effects of single nucleotide polymorphisms (SNPs) of PPARD on whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake in 129 healthy individuals using the hyperinsulinemic-euglycemic clamp technique combined with fluorine-18-labeled fluorodeoxyglucose ([(18)F]FDG) and positron emission tomography (PET) [33].
• MATERIALS AND METHODS: Primary beta cells that had been purified by fluorescence-activated cell sorting and INS-1E cells were cultured in the presence of the cytokines TNF-alpha, IL-1beta, or IL-1beta + IFN-gamma, or the synthetic PPAR-delta agonist GW501516 [34].
• Although differences in the genomic organization of the fish PPAR genes compared with their mammalian counterparts are evident, sequence alignments and phylogenetic comparisons show the fish genes to be homologs of mammalian PPARalpha, PPARbeta/delta, and PPARgamma [35].

References