Genomes and Genes
Gene Symbol: Ppard
Description: peroxisome proliferator activator receptor delta
Alias: NUC-1, NUC1, Nr1c2, PPAR-beta, PPAR-delta, PPAR[b], PPARdelta, Pparb, Pparb/d, peroxisome proliferator-activated receptor delta, PPARdelta/beta, Peroxisome proliferator-activated receptor beta, nuclear hormone receptor 1, nuclear receptor subfamily 1 group C member 2
- Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten M, van Bilsen M, Desvergne B, et al. Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress. Circ Res. 2010;106:1712-21 pubmed publisher..Stimulation of cardiac Angptl4 gene expression by dietary fatty acids and via PPARbeta/delta is part of a feedback mechanism aimed at protecting the heart against lipid overload and consequently fatty acid-induced oxidative stress. ..
- Foreman J, Sharma A, Amin S, Gonzalez F, Peters J. Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line. Cancer Lett. 2010;288:219-25 pubmed publisher..Results from this study show that proliferation of the C20 mouse mammary gland cancer cell line is inhibited by ligand activation of PPARbeta/delta due in part to increased apoptosis. ..
- Man M, Barish G, Schmuth M, Crumrine D, Barak Y, Chang S, et al. Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. J Invest Dermatol. 2008;128:370-7 pubmed..human keratinocytes or murine epidermis, peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) (NR1C2) activators (1) stimulate keratinocyte differentiation; (2) decrease keratinocyte proliferation; (3) accelerate ..
- Kim D, Murray I, Burns A, Gonzalez F, Perdew G, Peters J. Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity. J Biol Chem. 2005;280:9519-27 pubmed..Combined, these studies provide strong evidence that PPARbeta attenuates cell proliferation by modulating PKCalpha/Raf1/MEK/ERK activity that may be due in part to reduced ubiquitin-dependent turnover of PKCalpha. ..
- Marin H, Peraza M, Billin A, Willson T, Ward J, Kennett M, et al. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis. Cancer Res. 2006;66:4394-401 pubmed..of a PPARbeta ligand causes increased small intestinal tumorigenesis in Apc(min/+) mice, PPARbeta-null (Pparb-/-) mice exhibit increased colon polyp multiplicity in colon cancer bioassays, suggesting that ligand activation ..
- Narkar V, Downes M, Yu R, Embler E, Wang Y, Banayo E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134:405-15 pubmed publisher..These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance ..
- Muoio D, MacLean P, Lang D, Li S, Houmard J, Way J, et al. Fatty acid homeostasis and induction of lipid regulatory genes in skeletal muscles of peroxisome proliferator-activated receptor (PPAR) alpha knock-out mice. Evidence for compensatory regulation by PPAR delta. J Biol Chem. 2002;277:26089-97 pubmed..Real time quantitative PCR analyses showed that unlike in liver and heart, in mouse skeletal muscle PPAR delta is severalfold more abundant than either PPAR alpha or PPAR gamma...
- Dressel U, Allen T, Pippal J, Rohde P, Lau P, Muscat G. The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol. 2003;17:2477-93 pubmed
- Reed K, Sansom O, Hayes A, Gescher A, Winton D, Peters J, et al. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene. 2004;23:8992-6 pubmedBased on recent reports that peroxisome proliferator-activated receptor delta (PPARdelta) activation promotes tumourigenesis, we have investigated the role of this protein in Apc-mediated intestinal tumourigenesis...
- Ding G, Cheng L, Qin Q, Frontin S, Yang Q. PPARdelta modulates lipopolysaccharide-induced TNFalpha inflammation signaling in cultured cardiomyocytes. J Mol Cell Cardiol. 2006;40:821-8 pubmed..However, it remains obscured if PPARdelta and its ligands exert any effect on the production of TNFalpha, thus influencing cardiac inflammatory responses...
- 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. ..
- Schuler M, Ali F, Chambon C, Duteil D, Bornert J, Tardivel A, et al. PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes. Cell Metab. 2006;4:407-14 pubmed
- Gaudel C, Schwartz C, Giordano C, Abumrad N, Grimaldi P. Pharmacological activation of PPARbeta promotes rapid and calcineurin-dependent fiber remodeling and angiogenesis in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2008;295:E297-304 pubmed publisher..In conclusion, the data indicate that PPARbeta activation is associated with a calcineurin-dependent effect on muscle morphology that enhances the oxidative phenotype. ..
- Piqueras L, Sanz M, Perretti M, Morcillo E, Norling L, Mitchell J, et al. Activation of PPARbeta/delta inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release. J Leukoc Biol. 2009;86:115-22 pubmed publisher..Taken together, our results show that PPARbeta/delta modulates acute inflammation in vivo and in vitro under flow by targeting the neutrophil-endothelial cell interaction. ..
- Kliewer S, Forman B, Blumberg B, Ong E, Borgmeyer U, Mangelsdorf D, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 1994;91:7355-9 pubmed..These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms. ..
- Kim Y, Han H. High-glucose-induced prostaglandin E(2) and peroxisome proliferator-activated receptor delta promote mouse embryonic stem cell proliferation. Stem Cells. 2008;26:745-55 pubmed..Subsequently, high glucose-induced PGE(2) stimulated PPARdelta expression directly or through Akt phosphorylation indirectly through the E type prostaglandin receptor ..
- 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..Although the nuclear receptor PPARdelta has been implicated in both systemic lipid metabolism and macrophage inflammation, its role as a therapeutic ..
- 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..More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad ..
- Di Poï N, Ng C, Tan N, Yang Z, Hemmings B, Desvergne B, et al. Epithelium-mesenchyme interactions control the activity of peroxisome proliferator-activated receptor beta/delta during hair follicle development. Mol Cell Biol. 2005;25:1696-712 pubmed
- Yin K, Deng Z, Hamblin M, Zhang J, Chen Y. Vascular PPAR? protects against stroke-induced brain injury. Arterioscler Thromb Vasc Biol. 2011;31:574-81 pubmed publisher..The pharmacological activation of PPAR? may provide a new therapeutic strategy to treat stroke-induced vascular and neuronal damage. ..
- Wu H, Chen C, Cheng K, Li Y, Yeh C, Cheng J. Pharmacological activation of peroxisome proliferator-activated receptor ? improves insulin resistance and hepatic steatosis in high fat diet-induced diabetic mice. Horm Metab Res. 2011;43:631-5 pubmed publisher..Thus, we suggest that pharmacological activation of PPAR? may be a new strategy for the treatment of diabetic patients with hepatic steatosis. ..
- Sanderson L, Degenhardt T, Koppen A, Kalkhoven E, Desvergne B, Muller M, et al. Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver. Mol Cell Biol. 2009;29:6257-67 pubmed publisher..In contrast, this is not the case for PPARalpha, revealing a novel mechanism for functional differentiation between PPARs. ..
- 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. ..
- Di Poï N, Michalik L, Tan N, Desvergne B, Wahli W. The anti-apoptotic role of PPARbeta contributes to efficient skin wound healing. J Steroid Biochem Mol Biol. 2003;85:257-65 pubmed..Finally, comparison of PPARbeta and Akt1 knock-out mice reveals many similarities, and suggests that the ability of PPARbeta to modulate the Akt1 pathway has significant impact during skin wound healing. ..
- Cheng L, Ding G, Qin Q, Huang Y, Lewis W, He N, et al. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy. Nat Med. 2004;10:1245-50 pubmed..We suggest that PPAR-delta is a potential therapeutic target in treating lipotoxic cardiomyopathy and other heart diseases. ..
- Tanaka T, Yamamoto J, Iwasaki S, Asaba H, Hamura H, Ikeda Y, et al. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. Proc Natl Acad Sci U S A. 2003;100:15924-9 pubmedIn this study, we defined the role of peroxisome proliferator-activated receptor beta/delta (PPARdelta) in metabolic homeostasis by using subtype selective agonists...
- Chawla A, Lee C, Barak Y, He W, Rosenfeld J, Liao D, et al. PPARdelta is a very low-density lipoprotein sensor in macrophages. Proc Natl Acad Sci U S A. 2003;100:1268-73 pubmed..Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions. ..
- Luquet S, Lopez Soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, et al. Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability. FASEB J. 2003;17:2299-301 pubmed..The physiological functions of PPARdelta remain elusive...
- Lee C, Olson P, Hevener A, Mehl I, Chong L, Olefsky J, et al. PPARdelta regulates glucose metabolism and insulin sensitivity. Proc Natl Acad Sci U S A. 2006;103:3444-9 pubmed..We show that PPARdelta (NR1C2) knockout mice are metabolically less active and glucose-intolerant, whereas receptor activation in db/db ..
- Rosenberger T, Hovda J, Peters J. Targeted disruption of peroxisomal proliferator-activated receptor beta (delta) results in distinct gender differences in mouse brain phospholipid and esterified FA levels. Lipids. 2002;37:495-500 pubmed..These data suggest that PPARbeta is involved in maintaining FA and phospholipid levels in adult female mouse brain and provide strong evidence that suggests a role for PPARbeta in brain peroxisomal acyl-CoA utilization. ..
- Calléja C, Messaddeq N, Chapellier B, Yang H, Krezel W, Li M, et al. Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes. Genes Dev. 2006;20:1525-38 pubmed
- Nadra K, Anghel S, Joye E, Tan N, Basu Modak S, Trono D, et al. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta. Mol Cell Biol. 2006;26:3266-81 pubmed..Altogether, this important role of PPARbeta/delta in placenta development and giant cell differentiation should be considered when contemplating the potency of PPARbeta/delta agonist as therapeutic agents of broad application. ..
- Serrano Marco L, Rodríguez Calvo R, El Kochairi I, Palomer X, Michalik L, Wahli W, et al. Activation of peroxisome proliferator-activated receptor-?/-? (PPAR-?/-?) ameliorates insulin signaling and reduces SOCS3 levels by inhibiting STAT3 in interleukin-6-stimulated adipocytes. Diabetes. 2011;60:1990-9 pubmed publisher
- Ali F, Egan K, Fitzgerald G, Desvergne B, Wahli W, Bishop Bailey D, et al. Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts. Am J Respir Cell Mol Biol. 2006;34:242-6 pubmed..This study is the first to identify PPARbeta as a potential therapeutic target for the treatment of pulmonary hypertension, which is important because orally active PPARbeta ligands have been developed for the treatment of dyslipidemia. ..
- Dunn S, Bhat R, Straus D, Sobel R, Axtell R, Johnson A, et al. Peroxisome proliferator-activated receptor delta limits the expansion of pathogenic Th cells during central nervous system autoimmunity. J Exp Med. 2010;207:1599-608 pubmed publisher..Collectively, these findings suggest that PPAR-delta serves as an important molecular brake for the control of autoimmune inflammation. ..
- Vittoria Simonini M, Polak P, Boullerne A, Peters J, Richardson J, Feinstein D. Regulation of oligodendrocyte progenitor cell maturation by PPAR?: effects on bone morphogenetic proteins. ASN Neuro. 2010;2:e00025 pubmed publisher..In contrast, GW0742 reduced BMP2 and BMP4 mRNA levels in OPCs, with lesser effects in astrocytes. These findings demonstrate that PPAR? plays a role in OPC maturation, mediated, in part, by regulation of BMP and BMP antagonists. ..
- Zuo X, Peng Z, Moussalli M, Morris J, Broaddus R, Fischer S, et al. Targeted genetic disruption of peroxisome proliferator-activated receptor-delta and colonic tumorigenesis. J Natl Cancer Inst. 2009;101:762-7 pubmed publisher..Increased expression of vascular endothelial growth factor in colon tumors vs normal colon was suppressed by loss of PPAR-delta expression. These findings indicate that PPAR-delta has a crucial role in promoting colonic tumorigenesis. ..
- Romanowska M, al Yacoub N, Seidel H, Donandt S, Gerken H, Phillip S, et al. PPARdelta enhances keratinocyte proliferation in psoriasis and induces heparin-binding EGF-like growth factor. J Invest Dermatol. 2008;128:110-24 pubmed..exhibiting a pattern consistent with the activation of peroxisome proliferator-activated receptor delta (PPARdelta). PPARdelta itself was strongly induced in psoriasis in vivo...
- Barak Y, Liao D, He W, Ong E, Nelson M, Olefsky J, et al. Effects of peroxisome proliferator-activated receptor delta on placentation, adiposity, and colorectal cancer. Proc Natl Acad Sci U S A. 2002;99:303-8 pubmedTargeting of the nuclear prostaglandin receptor peroxisome proliferator-activated receptor delta (PPARdelta) by homologous recombination results in placental defects and frequent (>90%) midgestation lethality...
- Di Poï N, Tan N, Michalik L, Wahli W, Desvergne B. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell. 2002;10:721-33 pubmed..Together, these results provide a molecular mechanism by which PPARbeta protects keratinocytes against apoptosis and may contribute to the process of skin wound closure. ..
- Shan W, Palkar P, Murray I, McDevitt E, Kennett M, Kang B, et al. Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression. Toxicol Sci. 2008;105:418-28 pubmed publisher..Hepatocytes and hepatic stellate cells do not appear to directly mediate the inhibitory effects of ligand activation of PPARbeta/delta in liver, suggesting the involvement of paracrine and autocrine events mediated by hepatic cells. ..
- Kang K, Reilly S, Karabacak V, Gangl M, Fitzgerald K, Hatano B, et al. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab. 2008;7:485-95 pubmed publisher..adipocytes are a source of Th2 cytokines, including IL-13 and to a lesser extent IL-4, which induce macrophage PPARdelta/beta (Ppard/b) expression through a STAT6 binding site on its promoter to activate alternative activation...
- Zaveri N, Sato B, Jiang F, Calaoagan J, Laderoute K, Murphy B. A novel peroxisome proliferator-activated receptor delta antagonist, SR13904, has anti-proliferative activity in human cancer cells. Cancer Biol Ther. 2009;8:1252-61 pubmedThe peroxisome proliferator-activated receptor delta (PPARdelta) is a ligand-activated, nuclear receptor transcription factor that has a documented role in glucose and lipid homeostasis...
- Akiyama T, Lambert G, Nicol C, Matsusue K, Peters J, Brewer H, et al. Peroxisome proliferator-activated receptor beta/delta regulates very low density lipoprotein production and catabolism in mice on a Western diet. J Biol Chem. 2004;279:20874-81 pubmed
- Alvarez Guardia D, Palomer X, Coll T, Serrano L, Rodríguez Calvo R, Davidson M, et al. PPAR?/? activation blocks lipid-induced inflammatory pathways in mouse heart and human cardiac cells. Biochim Biophys Acta. 2011;1811:59-67 pubmed publisher..This is relevant, especially taking into account that PPAR?/? has been postulated as a potential target in the treatment of obesity and the insulin resistance state. ..
- Tan N, Michalik L, Noy N, Yasmin R, Pacot C, Heim M, et al. Critical roles of PPAR beta/delta in keratinocyte response to inflammation. Genes Dev. 2001;15:3263-77 pubmed..It is shown here, by use of cultures of primary keratinocytes from wild-type and PPAR beta/delta(-/-) mice, that such signals including TNF-alpha and IFN-gamma, induce keratinocyte differentiation...
- 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 pubmedPeroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes...
- Wang Y, Zhang C, Yu R, Cho H, Nelson M, Bayuga Ocampo C, et al. Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol. 2004;2:e294 pubmed..was achieved by targeted expression of an activated form of peroxisome proliferator-activated receptor delta (PPARdelta) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers...
- Harman F, Nicol C, Marin H, Ward J, Gonzalez F, Peters J. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med. 2004;10:481-3 pubmed..We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice...
- Kim D, Bility M, Billin A, Willson T, Gonzalez F, Peters J. PPARbeta/delta selectively induces differentiation and inhibits cell proliferation. Cell Death Differ. 2006;13:53-60 pubmed
- Takata Y, Liu J, Yin F, Collins A, Lyon C, Lee C, et al. PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc Natl Acad Sci U S A. 2008;105:4277-82 pubmed publisherActivation of the nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARdelta) has been shown to improve insulin resistance, adiposity, and plasma HDL levels...