Genomes and Genes
Gene Symbol: PPARD
Description: peroxisome proliferator activated receptor delta
Alias: FAAR, NR1C2, NUC1, NUCI, NUCII, PPARB, peroxisome proliferator-activated receptor delta, PPAR-beta, PPAR-delta, PPARD/MYO1D fusion, nuclear hormone receptor 1, nuclear receptor subfamily 1 group C member 2, peroxisome proliferator-activated receptor beta
- Grarup N, Albrechtsen A, Ek J, Borch Johnsen K, Jørgensen T, Schmitz O, et al. Variation in the peroxisome proliferator-activated receptor delta gene in relation to common metabolic traits in 7,495 middle-aged white people. Diabetologia. 2007;50:1201-8 pubmed..Thus, we hypothesised that common variation in the PPARD gene is associated with insulin resistance and metabolic traits...
- Schmuth M, Haqq C, Cairns W, Holder J, Dorsam S, Chang S, et al. Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes. J Invest Dermatol. 2004;122:971-83 pubmed..Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes. ..
- Lu L, Wu Y, Qi Q, Liu C, Gan W, Zhu J, et al. Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese. PLoS ONE. 2012;7:e34895 pubmed publisherPrevious studies have identified that variants in peroxisome proliferator-activated receptor PPAR-? (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations...
- Degenhardt T, Saramaki A, Malinen M, Rieck M, Väisänen S, Huotari A, et al. Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. J Mol Biol. 2007;372:341-55 pubmed..In conclusion, PDK2, PDK3 and PDK4 are primary PPARbeta/delta target genes in humans underlining the importance of the receptor in the control of metabolism. ..
- Zandi P, Belmonte P, Willour V, Goes F, Badner J, Simpson S, et al. Association study of Wnt signaling pathway genes in bipolar disorder. Arch Gen Psychiatry. 2008;65:785-93 pubmed publisher..Initial results led us to focus on the gene PPARD, in which we genotyped an additional 13 SNPs for follow-up. Nine academic medical centers in the United States...
- Gouni Berthold I, Giannakidou E, Faust M, Berthold H, Krone W. The peroxisome proliferator-activated receptor delta +294T/C polymorphism in relation to lipoprotein metabolism in patients with diabetes mellitus type 2 and in non-diabetic controls. Atherosclerosis. 2005;183:336-41 pubmed..The data suggest that the PPARdelta +294T/C polymorphism has no influence on plasma lipoprotein concentrations, body mass index or atherosclerotic disease either in healthy subjects or in patients with DM-2, both in males and females. ..
- Molnár F, Matilainen M, Carlberg C. Structural determinants of the agonist-independent association of human peroxisome proliferator-activated receptors with coactivators. J Biol Chem. 2005;280:26543-56 pubmed..This leads to high basal activity of PPARs and provides an additional view on PPAR signaling. ..
- Krämer D, Al Khalili L, Perrini S, Skogsberg J, Wretenberg P, Kannisto K, et al. Direct activation of glucose transport in primary human myotubes after activation of peroxisome proliferator-activated receptor delta. Diabetes. 2005;54:1157-63 pubmed..Moreover, we provide biological validation of PPARdelta as a potential target for antidiabetic therapy. ..
- Skogsberg J, McMahon A, Karpe F, Hamsten A, Packard C, Ehrenborg E. Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men. J Intern Med. 2003;254:597-604 pubmedb>Peroxisome proliferator activated receptor delta (PPARD) is a transcription factor implicated in the regulation of genes involved in cholesterol metabolism...
- Nikitin A, Chistiakov D, Minushkina L, Zateyshchikov D, Nosikov V. Association of the CYBA, PPARGC1A, PPARG3, and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population. Heart Vessels. 2010;25:229-36 pubmed publisher..In this study, we evaluate whether the PPARGC1A Gly482Ser, PPARG3 (-681)C/G, PPARD +294T/C, and CYBA +242C/T gene variants confer the risk of CAD in a Russian population...
- Ali F, Ali N, Bauer A, Boyle J, Hamdulay S, Haskard D, et al. PPARdelta and PGC1alpha act cooperatively to induce haem oxygenase-1 and enhance vascular endothelial cell resistance to stress. Cardiovasc Res. 2010;85:701-10 pubmed publisher..In light of the protective effects of haem oxygenase-1 against atherogenesis, we suggest that PPARdelta represents a potentially important therapeutic target in the vasculature. ..
- Aberle J, Hopfer I, Beil F, Seedorf U. Association of peroxisome proliferator-activated receptor delta +294T/C with body mass index and interaction with peroxisome proliferator-activated receptor alpha L162V. Int J Obes (Lond). 2006;30:1709-13 pubmed..Moreover an interaction between the polymorphisms in PPARalpha and PPARdelta on body weight could be demonstrated. Our data provide further evidence for an involvement of PPARdelta in the regulation of BMI. ..
- Hatae T, Wada M, Yokoyama C, Shimonishi M, Tanabe T. Prostacyclin-dependent apoptosis mediated by PPAR delta. J Biol Chem. 2001;276:46260-7 pubmed..kidney 293 cells promotes apoptosis by activating endogenous peroxisome proliferator-activated receptor delta (PPAR delta). In contrast, treatment of cells with extracellular prostacyclin or dibutyryl cAMP actually reduced apoptosis...
- Shin H, Park B, Kim L, Jung H, Cho Y, Moon M, et al. Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity. Diabetes. 2004;53:847-51 pubmed..The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases. ..
- Yang L, Zhang H, Zhou Z, Yan H, Adell G, Sun X. Biological function and prognostic significance of peroxisome proliferator-activated receptor ? in rectal cancer. Clin Cancer Res. 2011;17:3760-70 pubmed publisher..PPAR ? is related to the early development of rectal cancer and inhibits the proliferation of colorectal cancer cells. Increase of PPAR ? predicts favorable survival in the rectal cancer patients either with or without preoperative RT. ..
- Staiger H, Haas C, Machann J, Werner R, Weisser M, Schick F, et al. Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator-activated receptor (PPAR)-delta and is of metabolic relevance in humans. Diabetes. 2009;58:579-89 pubmed publisher..In C2C12 myocytes, knockdown of PPARD, but not of PPARG, blocked LCFA-mediated ANGPTL4 induction, and LCFA treatment resulted in PPAR-delta recruitment ..
- Xu H, Lambert M, Montana V, Parks D, Blanchard S, Brown P, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell. 1999;3:397-403 pubmed..We report the crystal structure of the PPAR delta ligand-binding domain (LBD) bound to either the FA eicosapentaenoic acid (EPA) or the synthetic fibrate GW2433...
- Adhikary T, Kaddatz K, Finkernagel F, Schönbauer A, Meissner W, Scharfe M, et al. Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-?/? (PPAR?/?). PLoS ONE. 2011;6:e16344 pubmed publisher..These observations have important implications for understanding the regulatory PPAR network and PPAR?/? ligand-based drugs. ..
- Akhmetov I, Astranenkova I, Rogozkin V. [Association of PPARD gene polymorphism with human physical performance]. Mol Biol (Mosk). 2007;41:852-7 pubmed..To examine the association of a functional +294T/C polymorphism of PPARD gene with human physical performance, we have studied the distribution of PPARD alleles and genotypes in a cohort ..
- Takahashi S, Tanaka T, Sakai J. New therapeutic target for metabolic syndrome: PPARdelta. Endocr J. 2007;54:347-57 pubmed
- Stefan N, Thamer C, Staiger H, Machicao F, Machann J, Schick F, et al. Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. J Clin Endocrinol Metab. 2007;92:1827-33 pubmed..Peroxisome proliferator-activated receptor (PPAR)-delta (gene PPARD) and PPARgamma coactivator 1alpha (gene PPARGC1A) are determinants of mitochondrial function in animals and in ..
- Bastie C, Luquet S, Holst D, Jehl Pietri C, Grimaldi P. Alterations of peroxisome proliferator-activated receptor delta activity affect fatty acid-controlled adipose differentiation. J Biol Chem. 2000;275:38768-73 pubmed..Furthermore, they suggest that modulation of PPARdelta expression or activity could affect adaptive responses of white adipose tissue to nutritional changes. ..
- Yan Z, Shen C, Zhong J, Wang L, Ni Y, Nie H, et al. [PPARdelta + 294T/C gene polymorphism related to plasma lipid, obesity and left ventricular hypertrophy in subjects with metabolic syndrome]. Zhonghua Xin Xue Guan Bing Za Zhi. 2005;33:529-33 pubmed..05). It is indicated that PPARdelta + 294T/C gene polymorphism in subjects with MS may be involved in the occurrence of obesity and dyslipidemia. MS patients with C allele had a predominant LVH than subjects with TT genotype. ..
- Barish G, Narkar V, Evans R. PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest. 2006;116:590-7 pubmed
- Yang L, Olsson B, Pfeifer D, Jonsson J, Zhou Z, Jiang X, et al. Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells. Oncogene. 2010;29:516-26 pubmed publisher..Interestingly, PPAR-beta seems to have a more important role in poorly metastatic cells than in highly metastatic ones. ..
- He T, Chan T, Vogelstein B, Kinzler K. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999;99:335-45 pubmedb>PPARB was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPARdelta expression was elevated in CRCs and repressed by APC in CRC cells...
- Skogsberg J, Kannisto K, Roshani L, Gagne E, Hamsten A, Larsson C, et al. Characterization of the human peroxisome proliferator activated receptor delta gene and its expression. Int J Mol Med. 2000;6:73-81 pubmed..Three different PPARs; alpha (PPARA), gamma (PPARG) and delta (PPARD) have been characterized and they are distinguished from each other by tissue distribution and cell activation...
- Robitaille J, Gaudet D, Perusse L, Vohl M. Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-delta -87T>C polymorphism and dietary fat in French-Canadians. Int J Obes (Lond). 2007;31:411-7 pubmed..The metabolic syndrome (MS) is influenced by genetic and environmental factors. Peroxisome proliferator-activated receptor delta (PPAR-delta), a transcription factor involved in lipid metabolism, is a candidate gene for the MS. ..
- Fauconnet S, Lascombe I, Chabannes E, Adessi G, Desvergne B, Wahli W, et al. Differential regulation of vascular endothelial growth factor expression by peroxisome proliferator-activated receptors in bladder cancer cells. J Biol Chem. 2002;277:23534-43 pubmed..They may lead to a new therapeutic approach to human bladder cancer in which excessive angiogenesis is a negative prognostic factor. ..
- Peters J, Lee S, Li W, Ward J, Gavrilova O, Everett C, et al. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol. 2000;20:5119-28 pubmed..These results are the first to provide in vivo evidence of significant roles for PPARbeta in development, myelination of the corpus callosum, lipid metabolism, and epidermal cell proliferation. ..
- Krogsdam A, Nielsen C, Neve S, Holst D, Helledie T, Thomsen B, et al. Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation. Biochem J. 2002;363:157-65 pubmed..NCoR interacted strongly with the ligand-binding domain of PPAR delta, whereas interactions with the ligand-binding domains of PPAR gamma and PPAR alpha were significantly weaker...
- Kaddatz K, Adhikary T, Finkernagel F, Meissner W, Müller Brüsselbach S, Muller R. Transcriptional profiling identifies functional interactions of TGF ? and PPAR ?/? signaling: synergistic induction of ANGPTL4 transcription. J Biol Chem. 2010;285:29469-79 pubmed publisher..Although the PPAR-E is not regulated by TGF?, it interacts with SMAD3, ETS1, RUNX2, and AP-1 in vivo, providing a possible mechanistic explanation for the observed synergism. ..
- Lagou V, Scott R, Manios Y, Chen T, Wang G, Grammatikaki E, et al. Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study. Obesity (Silver Spring). 2008;16:913-8 pubmed publisher..proliferator-activated receptor gamma (PPAR gamma) and peroxisome proliferator-activated receptor delta (PPAR delta) are promising candidate genes for obesity...
- Fritz T, Krämer D, Karlsson H, Galuska D, Engfeldt P, Zierath J, et al. Low-intensity exercise increases skeletal muscle protein expression of PPARdelta and UCP3 in type 2 diabetic patients. Diabetes Metab Res Rev. 2006;22:492-8 pubmed..These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes. ..
- Riserus U, Sprecher D, Johnson T, Olson E, Hirschberg S, Liu A, et al. Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men. Diabetes. 2008;57:332-9 pubmed..The PPARdelta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle. ..
- Genini D, Catapano C. Block of nuclear receptor ubiquitination. A mechanism of ligand-dependent control of peroxisome proliferator-activated receptor delta activity. J Biol Chem. 2007;282:11776-85 pubmed
- Thamer C, Machann J, Stefan N, Schäfer S, Machicao F, Staiger H, et al. Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. J Clin Endocrinol Metab. 2008;93:1497-500 pubmed publisher..that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e...
- Yang L, Zhou Z, Luo H, Zhou B, Xia Q, Tian C. Quantitative analysis of PPARdelta mRNA by real-time RT-PCR in 86 rectal cancer tissues. Eur J Surg Oncol. 2006;32:181-5 pubmed..However, the general level of PPARdelta mRNA in rectal cancer tissues is not statistically different from normal mucosa. The expression of PPARdelta gene in rectal cancers is not statistically different from normal mucosa. ..
- Shi Y, Hon M, Evans R. The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. Proc Natl Acad Sci U S A. 2002;99:2613-8 pubmed
- Chong H, Tan M, Philippe V, Tan S, Tan C, Ku C, et al. Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing. J Cell Biol. 2009;184:817-31 pubmed publisher..Given the ubiquitous expression of PPARbeta/delta, other epithelial-mesenchymal interactions may also be regulated in a similar manner. ..
- Tsai M, Chen L, Zhou J, Tang Z, Hsu T, Wang Y, et al. Shear stress induces synthetic-to-contractile phenotypic modulation in smooth muscle cells via peroxisome proliferator-activated receptor alpha/delta activations by prostacyclin released by sheared endothelial cells. Circ Res. 2009;105:471-80 pubmed publisher..Our findings provide insights into the mechanisms underlying the EC-SMC interplays and the protective homeostatic function of laminar shear stress in modulating SMC phenotype. ..
- Wang D, Wang H, Guo Y, Ning W, Katkuri S, Wahli W, et al. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. Proc Natl Acad Sci U S A. 2006;103:19069-74 pubmed
- Lee C, Chawla A, Urbiztondo N, Liao D, Boisvert W, Evans R, et al. Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science. 2003;302:453-7 pubmed..PPARdelta and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis. ..
- Barish G, Atkins A, Downes M, Olson P, Chong L, Nelson M, et al. PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis. Proc Natl Acad Sci U S A. 2008;105:4271-6 pubmed publisher..These results reveal that PPARdelta antagonizes multiple proinflammatory pathways and suggest PPARdelta-selective drugs as candidate therapeutics for atherosclerosis. ..
- Skogsberg J, Kannisto K, Cassel T, Hamsten A, Eriksson P, Ehrenborg E. Evidence that peroxisome proliferator-activated receptor delta influences cholesterol metabolism in men. Arterioscler Thromb Vasc Biol. 2003;23:637-43 pubmedThe objective of this work was to explore the role of peroxisome proliferator-activated receptor delta (PPARD) in lipid metabolism in humans. PPARD is a nuclear receptor involved in lipid metabolism in primates and mice...
- Ehrenborg E, Krook A. Regulation of skeletal muscle physiology and metabolism by peroxisome proliferator-activated receptor delta. Pharmacol Rev. 2009;61:373-93 pubmed publisher..In this review we summarize the current status regarding the regulation, and the metabolic effects, of PPARdelta in skeletal muscle. ..
- Park B, Vogelstein B, Kinzler K. Genetic disruption of PPARdelta decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci U S A. 2001;98:2598-603 pubmed..These data suggest that suppression of PPARdelta expression contributes to the growth-inhibitory effects of the APC tumor suppressor. ..
- Hautala A, Leon A, Skinner J, Rao D, Bouchard C, Rankinen T. Peroxisome proliferator-activated receptor-delta polymorphisms are associated with physical performance and plasma lipids: the HERITAGE Family Study. Am J Physiol Heart Circ Physiol. 2007;292:H2498-505 pubmed..DNA sequence variation in the PPARdelta locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL-C in healthy individuals in response to regular exercise. ..
- Aberle J, Hopfer I, Beil F, Seedorf U. Association of the T+294C polymorphism in PPAR delta with low HDL cholesterol and coronary heart disease risk in women. Int J Med Sci. 2006;3:108-11 pubmed..Our data show for the first time that the PPARdelta +T294C polymorphism is associated with lipid levels and coronary heart disease in women. However, the molecular mechanism of action remains to be elucidated. ..
- Yoshinaga M, Taki K, Somada S, Sakiyama Y, Kubo N, Kaku T, et al. The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients. Dig Dis Sci. 2011;56:1194-200 pubmed publisher..01). The expression of both PPAR ? and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients. ..
- Bouhlel M, Brozek J, Derudas B, Zawadzki C, Jude B, Staels B, et al. Unlike PPARgamma, PPARalpha or PPARbeta/delta activation does not promote human monocyte differentiation toward alternative macrophages. Biochem Biophys Res Commun. 2009;386:459-62 pubmed publisher..Thus, PPARalpha and PPARbeta/delta do not appear to modulate the alternative differentiation of human macrophages. ..
- Liang Y, Liu Y, Chen C, Lai L, Shyu K, Juang S, et al. Comparison of PPAR? and PPAR? in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells. Int J Cardiol. 2010;143:361-7 pubmed publisher..The results suggest that PPAR? attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-?B pathway. PPAR? may serve as a more potent therapeutic target than PPAR? in atherosclerosis or inflammatory therapy. ..
- Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature. 2000;405:421-4 pubmed..Here we present the latest developments in the PPAR field, with particular emphasis on the physiological function of PPARs during various nutritional states, and the possible role of PPARs in several chronic diseases. ..
- Holzapfel J, Heun R, Lutjohann D, Jessen F, Maier W, Kolsch H. PPARD haplotype influences cholesterol metabolism but is no risk factor of Alzheimer's disease. Neurosci Lett. 2006;408:57-61 pubmed..three frequent polymorphisms located in exons 4 (rs2016520) and 9 (rs3734254 and rs9794) of the PPARdelta gene (PPARD) for their putative influence on the risk of AD and on plasma levels of cholesterol, 24S-hydroxycholesterol and 27-..
- Mukundan L, Odegaard J, Morel C, Heredia J, Mwangi J, Ricardo Gonzalez R, et al. PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance. Nat Med. 2009;15:1266-72 pubmed publisher..This increases autoantibody production and predisposes global and macrophage-specific Ppard(-/-) mice to autoimmune kidney disease, a phenotype resembling the human disease systemic lupus erythematosus...
- Pedchenko T, Gonzalez A, Wang D, DuBois R, Massion P. Peroxisome proliferator-activated receptor beta/delta expression and activation in lung cancer. Am J Respir Cell Mol Biol. 2008;39:689-96 pubmed publisher..In conclusion, PPARbeta/delta is strongly expressed in the majority of lung cancers, and its activation induces proliferative and survival response in non-small cell lung cancer. ..