ppar delta


Summary: A nuclear transcription factor. It is activated by PROSTACYCLIN.

Top Publications

  1. 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
  2. Berry D, Noy N. All-trans-retinoic acid represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor beta/delta and retinoic acid receptor. Mol Cell Biol. 2009;29:3286-96 pubmed publisher
    ..By targeting two nuclear receptors, RA may be a uniquely efficacious agent in the therapy and prevention of the metabolic syndrome. ..
  3. Kanakasabai S, Chearwae W, Walline C, Iams W, Adams S, Bright J. Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology. 2010;130:572-88 pubmed publisher
    ..These findings indicate that PPARdelta agonists modulate Th1 and Th17 responses in EAE and suggest their use in the treatment of MS and other autoimmune diseases. ..
  4. 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. ..
  5. Coll T, Alvarez Guardia D, Barroso E, Gomez Foix A, Palomer X, Laguna J, et al. Activation of peroxisome proliferator-activated receptor-{delta} by GW501516 prevents fatty acid-induced nuclear factor-{kappa}B activation and insulin resistance in skeletal muscle cells. Endocrinology. 2010;151:1560-9 pubmed publisher
    ..Our results point to PPARdelta activation as a pharmacological target to prevent insulin resistance. ..
  6. Brown J, Oligino E, Rader D, Saghatelian A, Plutzky J. VLDL hydrolysis by hepatic lipase regulates PPAR? transcriptional responses. PLoS ONE. 2011;6:e21209 pubmed publisher
    ..These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription. ..
  7. Sprecher D, Massien C, Pearce G, Billin A, Perlstein I, Willson T, et al. Triglyceride:high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor delta agonist. Arterioscler Thromb Vasc Biol. 2007;27:359-65 pubmed
    ..In parallel, PPARdelta agonist-upregulated FAO would induce fatty-acid uptake (via peripheral lipolysis), and influence HDLc and TG-rich lipoprotein particle metabolism, as suggested in preclinical models...
  8. Li Y, Cheng L, Qin Q, Liu J, Lo W, Brako L, et al. High-fat feeding in cardiomyocyte-restricted PPARdelta knockout mice leads to cardiac overexpression of lipid metabolic genes but fails to rescue cardiac phenotypes. J Mol Cell Cardiol. 2009;47:536-43 pubmed publisher
    ..Increased lipid intake activates cardiac expression of FAO genes via PPARalpha/PGC-1alpha pathway, albeit it is not sufficient to improve cardiac pathology due to PPARdelta deficiency. ..
  9. Cohen G, Riahi Y, Shamni O, Guichardant M, Chatgilialoglu C, Ferreri C, et al. Role of lipid peroxidation and PPAR-? in amplifying glucose-stimulated insulin secretion. Diabetes. 2011;60:2830-42 pubmed publisher
    ..Elevated glucose levels augment the release of AA and LA from phospholipids and their peroxidation to 4-HNE in ?-cells. This molecule is an endogenous ligand for PPAR-?, which amplifies insulin secretion in ?-cells. ..

More Information


  1. 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. ..
  2. Toth P, Naruhn S, Pape V, Dörr S, Klebe G, Muller R, et al. Development of improved PPAR?/? inhibitors. ChemMedChem. 2012;7:159-70 pubmed publisher
    ..Additionally, the subtype-specific inhibition of PPAR?/? was confirmed in a cell-based assay making these compounds invaluable tools for the further exploration of the functions of PPAR?/?. ..
  3. Gustafsson M, Knight D, Palmer C. Ligand modulated antagonism of PPARgamma by genomic and non-genomic actions of PPARdelta. PLoS ONE. 2009;4:e7046 pubmed publisher
  4. Bility M, Devlin Durante M, Blazanin N, Glick A, Ward J, Kang B, et al. Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) inhibits chemically induced skin tumorigenesis. Carcinogenesis. 2008;29:2406-14 pubmed publisher
    ..These studies suggest that topical administration of PPARbeta/delta ligands may be useful as both a chemopreventive and/or a chemotherapeutic approach to inhibit skin cancer. ..
  5. 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. ..
  6. 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. ..
  7. Chen Z, Yu B, Chen L, Cheng K, Lin H, Cheng J. Characterization of the mechanisms of the increase in PPAR? expression induced by digoxin in the heart using the H9c2 cell line. Br J Pharmacol. 2011;163:390-8 pubmed publisher
    ..Similar changes were observed on the contraction of H9c2 cells. The results suggest that digoxin appears, through calcium-triggered signals, to reverse the reduced expression of PPAR? in H9c2 cells caused by HG treatment. ..
  8. Borland M, Khozoie C, Albrecht P, Zhu B, Lee C, Lahoti T, et al. Stable over-expression of PPAR?/? and PPAR? to examine receptor signaling in human HaCaT keratinocytes. Cell Signal. 2011;23:2039-50 pubmed publisher
  9. Yu B, Chang C, Ou H, Cheng K, Cheng J. Decrease of peroxisome proliferator-activated receptor delta expression in cardiomyopathy of streptozotocin-induced diabetic rats. Cardiovasc Res. 2008;80:78-87 pubmed publisher
    ..Our results suggest that inhibitors of ROS production or MAPK activation are involved in reduction of cardiac PPARdelta expression in response to hyperglycaemia. ..
  10. Zingarelli B, Piraino G, Hake P, O Connor M, Denenberg A, Fan H, et al. Peroxisome proliferator-activated receptor {delta} regulates inflammation via NF-{kappa}B signaling in polymicrobial sepsis. Am J Pathol. 2010;177:1834-47 pubmed publisher
    ..These data suggest that PPAR? is a crucial anti-inflammatory regulator, providing a basis for novel sepsis therapies...
  11. Pan D, Fujimoto M, Lopes A, Wang Y. Twist-1 is a PPARdelta-inducible, negative-feedback regulator of PGC-1alpha in brown fat metabolism. Cell. 2009;137:73-86 pubmed publisher
    ..These findings reveal an unexpected physiological role for twist-1 in the maintenance of energy homeostasis and have important implications for understanding metabolic control and metabolic diseases. ..
  12. 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 conclusion, the CYBA +242C/T and PPARD +294T/C variants modulate risk of CAD through their associations with atherogenic serum lipid profiles. ..
  13. Jiang Y, Uchida Y, Lu B, Kim P, Mao C, Akiyama M, et al. Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes. J Biol Chem. 2009;284:18942-52 pubmed publisher
  14. Kim H, Kim M, Jin H, Kim H, Kang S, Kim H, et al. Peroxisome proliferator-activated receptor {delta} regulates extracellular matrix and apoptosis of vascular smooth muscle cells through the activation of transforming growth factor-{beta}1/Smad3. Circ Res. 2009;105:16-24 pubmed publisher
    ..Specific ligands of PPARdelta may aid in the therapeutic intervention of atherosclerosis by improving plaque stability and patient prognosis. ..
  15. Bays H, Schwartz S, Littlejohn T, Kerzner B, Krauss R, Karpf D, et al. MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin. J Clin Endocrinol Metab. 2011;96:2889-97 pubmed publisher
    ..MBX-8025 also reduced liver enzyme levels. MBX-8025, a novel PPAR-? agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study. ..
  16. Marsillach J, Camps J, Ferre N, Beltran R, Rull A, Mackness B, et al. Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease. BMC Gastroenterol. 2009;9:3 pubmed publisher
    ..005) and between PON1 and the amount of activated stellate cells (P = 0.001). Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1. ..
  17. 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. ..
  18. 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
    ..If the finding can be confirmed in additional samples, it may illuminate a new avenue for understanding the pathogenesis of severe bipolar disorder and developing more effective treatments. ..
  19. Peters J, Hollingshead H, Gonzalez F. Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease. Clin Sci (Lond). 2008;115:107-27 pubmed publisher
    ..In the present review, we summarize the role of PPARbeta/delta in gastrointestinal physiology and disease with an emphasis on findings in experimental models using both high-affinity ligands and null-mouse models. ..
  20. Di Paola R, Esposito E, Mazzon E, Paterniti I, Galuppo M, Cuzzocrea S. GW0742, a selective PPAR-beta/delta agonist, contributes to the resolution of inflammation after gut ischemia/reperfusion injury. J Leukoc Biol. 2010;88:291-301 pubmed publisher
    ..Based on these findings, we propose that GW0742 would be useful in the treatment of various I/R diseases. ..
  21. Fan S, Yu B, Chen Z, Chen L, Chung H, Cheng J. The decreased expression of peroxisome proliferator-activated receptors delta (PPARdelta) is reversed by digoxin in the heart of diabetic rats. Horm Metab Res. 2010;42:637-42 pubmed publisher
    ..The increase of cardiac output by digoxin was reversed by the combined treatment with PPARdelta antagonist GSK0660. Thus, we suggest a new finding that PPARdelta is involved in digoxin induced cardiac inrotropic action. ..
  22. Yang X, Kume S, Tanaka Y, Isshiki K, Araki S, Chin Kanasaki M, et al. GW501516, a PPAR? agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NF?B pathway in mice. PLoS ONE. 2011;6:e25271 pubmed publisher
    ..In conclusion, we demonstrate that GW501516 has an anti-inflammatory effect in renal tubular cells and may serve as a therapeutic candidate to attenuate tubulointerstitial lesions in proteinuric kidney diseases. ..
  23. He P, Borland M, Zhu B, Sharma A, Amin S, El Bayoumy K, et al. Effect of ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in human lung cancer cell lines. Toxicology. 2008;254:112-7 pubmed publisher
  24. Miao L, Yin R, Wu D, Cao X, Li Q, Hu X, et al. Peroxisome proliferator-activated receptor delta +294T > C polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Lipids Health Dis. 2010;9:145 pubmed publisher
    ..The discrepancy between the two ethnic groups might partly result from different PPARD +294T > C polymorphism or PPARD gene-environmental interactions. ..
  25. Schuster M, Zouboulis C, Ochsendorf F, Muller J, Thaci D, Bernd A, et al. Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne?. Br J Dermatol. 2011;164:182-6 pubmed publisher
    ..The present data suggest that activators of PPAR, in particular of the ? subset, might have beneficial effects on acne vulgaris by inhibiting the release of lipids in the context of sebocyte apoptosis. ..
  26. 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. ..
  27. Kalinin S, Richardson J, Feinstein D. A PPARdelta agonist reduces amyloid burden and brain inflammation in a transgenic mouse model of Alzheimer's disease. Curr Alzheimer Res. 2009;6:431-7 pubmed
    ..These results suggest that, as found for some PPARgamma agonists, PPARdelta agonists can also reduce amyloid burden likely to be mediated by effects on amyloid clearance. ..
  28. Bishop Bailey D, Bystrom J. Emerging roles of peroxisome proliferator-activated receptor-beta/delta in inflammation. Pharmacol Ther. 2009;124:141-50 pubmed publisher
    ..In contrast, the roles of PPARbeta/delta regulating inflammation and immunity are only just emerging. This review will focus on these emerging roles of PPARbeta/delta in regulating inflammatory processes. ..
  29. Zhu B, Khozoie C, Bility M, Ferry C, Blazanin N, Glick A, et al. Peroxisome proliferator-activated receptor ?/? cross talks with E2F and attenuates mitosis in HRAS-expressing cells. Mol Cell Biol. 2012;32:2065-82 pubmed publisher
  30. Naruhn S, Meissner W, Adhikary T, Kaddatz K, Klein T, Watzer B, et al. 15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor beta/delta agonist. Mol Pharmacol. 2010;77:171-84 pubmed publisher
    ..Both 15R-HETE and 15S-HETE are similarly potent at inducing PPARbeta/delta coactivator binding and transcriptional activation, indicating that 15-HETE enantiomers generated by different pathways function as PPARbeta/delta agonists. ..
  31. Quintela A, Jimenez R, Gómez Guzmán M, Zarzuelo M, Galindo P, Sanchez M, et al. Activation of peroxisome proliferator-activated receptor-?/-? (PPAR?/?) prevents endothelial dysfunction in type 1 diabetic rats. Free Radic Biol Med. 2012;53:730-41 pubmed publisher
    ..This effect seems to be related to an increase in nitric oxide bioavailability as a result of reduced NADPH oxidase-driven superoxide production and downregulation of prepro endothelin-1. ..
  32. Winzell M, Wulff E, Olsen G, Sauerberg P, Gotfredsen C, Ahren B. Improved insulin sensitivity and islet function after PPARdelta activation in diabetic db/db mice. Eur J Pharmacol. 2010;626:297-305 pubmed publisher
    ..This suggests that activation of PPARdelta improves glucose metabolism and may therefore potentially be target for treatment of type 2 diabetes. ..
  33. Lim H, Lee S, Park J, Lee K, Choi H, Chung K, et al. PPAR delta agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cell cycle. Atherosclerosis. 2009;202:446-54 pubmed publisher
    ..b>PPAR delta is ubiquitously expressed and involved in lipid and glucose metabolism...
  34. Haskova Z, Hoang B, Luo G, Morgan L, Billin A, Barone F, et al. Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742. Inflamm Res. 2008;57:314-21 pubmed publisher
  35. Peters J, Gonzalez F. Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer. Biochim Biophys Acta. 2009;1796:230-41 pubmed publisher
    ..Suggestions are offered to standardize measurements associated with these studies so that interlaboratory comparisons can be accurately assessed. ..
  36. Cresser J, Bonen A, Chabowski A, Stefanyk L, Gulli R, Ritchie I, et al. Oral administration of a PPAR-delta agonist to rodents worsens, not improves, maximal insulin-stimulated glucose transport in skeletal muscle of different fibers. Am J Physiol Regul Integr Comp Physiol. 2010;299:R470-9 pubmed publisher
    ..However, an accumulation of diacylglycerol and ceramide, while associated with diet-induced insulin resistance, does not appear to be responsible for the agonist-induced reduction in insulin-stimulated glucose transport. ..
  37. Rieck M, Meissner W, Ries S, Müller Brüsselbach S, Muller R. Ligand-mediated regulation of peroxisome proliferator-activated receptor (PPAR) beta/delta: a comparative analysis of PPAR-selective agonists and all-trans retinoic acid. Mol Pharmacol. 2008;74:1269-77 pubmed publisher
  38. 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. ..
  39. Riahi Y, Sin Malia Y, Cohen G, Alpert E, Gruzman A, Eckel J, et al. The natural protective mechanism against hyperglycemia in vascular endothelial cells: roles of the lipid peroxidation product 4-hydroxydodecadienal and peroxisome proliferator-activated receptor delta. Diabetes. 2010;59:808-18 pubmed publisher
    ..Collectively, our data show that 4-HDDE plays a central role in the downregulation of glucose uptake in VECs by activating PPARdelta. ..
  40. Matsushita Y, Ogawa D, Wada J, Yamamoto N, Shikata K, Sato C, et al. Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice. Diabetes. 2011;60:960-8 pubmed publisher
    ..These findings uncover a previously unrecognized mechanism for the renoprotective effects of PPAR? agonists and support the concept that PPAR? agonists may offer a novel therapeutic approach for the treatment of diabetic nephropathy. ..
  41. Wang P, Liu J, Li Y, Wu S, Luo J, Yang H, et al. Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res. 2010;106:911-9 pubmed publisher
    ..PPARdelta is an essential regulator of cardiac mitochondrial protection and biogenesis and PPARdelta activation can be a potential therapeutic target for cardiac disorders. ..
  42. Wagner K, Wagner N. Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions. Pharmacol Ther. 2010;125:423-35 pubmed publisher
    ..We will focus here on functions of PPARbeta in adipose tissue, skeletal muscle, heart, angiogenesis and cancer related to modifications in metabolism and the identified underlying molecular mechanisms. ..
  43. Chou M, Lo S, Cheng K, Li Y, Chen L, Cheng J. Activation of ?-adrenoceptors by dobutamine may induce a higher expression of peroxisome proliferator-activated receptors ? (PPAR?) in neonatal rat cardiomyocytes. ScientificWorldJournal. 2012;2012:248320 pubmed publisher
    ..Moreover, deletion of PPAR? using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPAR? is increased by dobutamine in cardiac cells...
  44. Salvi N, Guellich A, Michelet P, Demoule A, Le Guen M, Renou L, et al. Upregulation of PPARbeta/delta is associated with structural and functional changes in the type I diabetes rat diaphragm. PLoS ONE. 2010;5:e11494 pubmed publisher
  45. Liang Y, Chen C, Juang S, Lai L, Shyu K, Wang B, et al. Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts. Eur J Pharmacol. 2010;643:84-92 pubmed publisher
    ..However, PPARdelta activation attenuated CRP-induced NF-kappaB pathway may be independent of CD32. These results may provide new evidence of PPARdelta beneficial effects for inflammatory cardiomyopathy. ..
  46. 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 without exercise. ..
  47. Altieri P, Spallarossa P, Barisione C, Garibaldi S, Garuti A, Fabbi P, et al. Inhibition of doxorubicin-induced senescence by PPAR? activation agonists in cardiac muscle cells: cooperation between PPAR? and Bcl6. PLoS ONE. 2012;7:e46126 pubmed publisher
    ..This study increases our understanding of the molecular mechanism of anthracycline cardiotoxicity and suggests a potential role for PPAR? agonists as cardioprotective agents. ..
  48. 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. ..
  49. Jiang L, Wan J, Ke L, Lü Q, Tong N. Activation of PPAR? promotes mitochondrial energy metabolism and decreases basal insulin secretion in palmitate-treated ?-cells. Mol Cell Biochem. 2010;343:249-56 pubmed publisher
  50. Peters J, Foreman J, Gonzalez F. Dissecting the role of peroxisome proliferator-activated receptor-?/? (PPAR?/?) in colon, breast, and lung carcinogenesis. Cancer Metastasis Rev. 2011;30:619-40 pubmed publisher
    ..This review examines studies reporting the role of PPAR?/? in colon, breast, and lung cancers. The prevailing evidence would suggest that targeting PPAR?/? is not only safe but could have anti-carcinogenic protective effects. ..
  51. 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. ..
  52. Coll T, Rodríguez Calvo R, Barroso E, Serrano L, Eyre E, Palomer X, et al. Peroxisome proliferator-activated receptor (PPAR) beta/delta: a new potential therapeutic target for the treatment of metabolic syndrome. Curr Mol Pharmacol. 2009;2:46-55 pubmed
    ..However, clinical trials in humans assessing the efficacy and safety of these drugs should confirm these promising perspectives in the treatment of the metabolic syndrome. ..
  53. Scholtysek C, Katzenbeisser J, Fu H, Uderhardt S, Ipseiz N, Stoll C, et al. PPAR?/? governs Wnt signaling and bone turnover. Nat Med. 2013;19:608-13 pubmed publisher
    ..Our findings identify PPAR?/? as a promising target for an alternative approach in the treatment of osteoporosis and related diseases. ..
  54. Stockert J, Adhikary T, Kaddatz K, Finkernagel F, Meissner W, Müller Brüsselbach S, et al. Reverse crosstalk of TGF? and PPAR?/? signaling identified by transcriptional profiling. Nucleic Acids Res. 2011;39:119-31 pubmed publisher
    ..These observations indicate that PPAR?/? is able to influence the expression of distinct sets of both TGF?-repressed and TGF?-activated genes in both directions. ..
  55. Barroso E, Eyre E, Palomer X, Vázquez Carrera M. The peroxisome proliferator-activated receptor ?/? (PPAR?/?) agonist GW501516 prevents TNF-?-induced NF-?B activation in human HaCaT cells by reducing p65 acetylation through AMPK and SIRT1. Biochem Pharmacol. 2011;81:534-43 pubmed publisher
  56. 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. ..
  57. He T, Smith L, Lu T, Joyner M, Katusic Z. Activation of peroxisome proliferator-activated receptor-{delta} enhances regenerative capacity of human endothelial progenitor cells by stimulating biosynthesis of tetrahydrobiopterin. Hypertension. 2011;58:287-94 pubmed publisher
    ..Thus, in human EPCs, activation of PPAR? stimulates expression and activity of GTPCH I and biosynthesis of tetrahydrobiopterin via PTEN-AKT signaling pathway. This effect enhances the regenerative function of EPCs. ..
  58. Naruhn S, Toth P, Adhikary T, Kaddatz K, Pape V, Dörr S, et al. High-affinity peroxisome proliferator-activated receptor ?/?-specific ligands with pure antagonistic or inverse agonistic properties. Mol Pharmacol. 2011;80:828-38 pubmed publisher
    ..The possibility to differentially modulate specific functions of PPAR?/? makes these novel compounds invaluable tools to advance our understanding of PPAR?/? biology. ..
  59. Shearer B, Wiethe R, Ashe A, Billin A, Way J, Stanley T, et al. Identification and characterization of 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), a selective and irreversible peroxisome proliferator-activated receptor delta (PPARdelta) antagonist. J Med Chem. 2010;53:1857-61 pubmed publisher
    ..Compound 3 is a PPARdelta antagonist with utility as a tool to elucidate PPARdelta cell biology and pharmacology. ..
  60. Qin X, Xie X, Fan Y, Tian J, Guan Y, Wang X, et al. Peroxisome proliferator-activated receptor-delta induces insulin-induced gene-1 and suppresses hepatic lipogenesis in obese diabetic mice. Hepatology. 2008;48:432-41 pubmed publisher
    ..Our study reveals a novel mechanism by which PPARdelta regulates lipogenesis, suggesting potential therapeutic applications of PPARdelta modulators in obesity and type 2 diabetes, as well as related steatotic liver diseases. ..
  61. Han J, Lee H, Yang H, Hur J, Jun S, Kim J, et al. Peroxisome proliferator-activated receptor-delta agonist enhances vasculogenesis by regulating endothelial progenitor cells through genomic and nongenomic activations of the phosphatidylinositol 3-kinase/Akt pathway. Circulation. 2008;118:1021-33 pubmed publisher
    ..The results of our study suggest that PPAR-delta agonist has therapeutic vasculogenic potential for the treatment of ischemic cardiovascular diseases. ..
  62. Benetti E, Patel N, Collino M. The role of PPAR?/? in the management of metabolic syndrome and its associated cardiovascular complications. Endocr Metab Immune Disord Drug Targets. 2011;11:273-84 pubmed
    ..This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR?/? agonists in the treatment of metabolic syndrome and its associated cardiovascular risk factors. ..
  63. Karpe F, Ehrenborg E. PPARdelta in humans: genetic and pharmacological evidence for a significant metabolic function. Curr Opin Lipidol. 2009;20:333-6 pubmed publisher
    ..Considering the hypolipidaemic effect in humans by PPARdelta agonists, long-term studies are needed to confirm efficacy and safety. ..
  64. 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
    ..These findings provide a molecular basis to modulate tissue-resident macrophage activation and insulin sensitivity. ..
  65. Ghosh M, Ai Y, Narko K, Wang Z, Peters J, Hla T. PPARdelta is pro-tumorigenic in a mouse model of COX-2-induced mammary cancer. Prostaglandins Other Lipid Mediat. 2009;88:97-100 pubmed publisher
    ..We postulate that activation of the nuclear receptor PPARdelta by COX-2-derived prostanoids may be involved in the proliferation of mammary epithelial cells and therefore contribute to mammary cancer development. ..
  66. 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. ..
  67. Kapoor A, Collino M, Castiglia S, Fantozzi R, Thiemermann C. Activation of peroxisome proliferator-activated receptor-beta/delta attenuates myocardial ischemia/reperfusion injury in the rat. Shock. 2010;34:117-24 pubmed publisher
  68. Ooi E, Watts G, Sprecher D, Chan D, Barrett P. Mechanism of action of a peroxisome proliferator-activated receptor (PPAR)-delta agonist on lipoprotein metabolism in dyslipidemic subjects with central obesity. J Clin Endocrinol Metab. 2011;96:E1568-76 pubmed publisher
    ..This study elucidates the mechanism of action of this PPAR-? agonist on lipoprotein metabolism and supports its potential use in treating dyslipidemia in obesity. ..
  69. 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. ..
  70. 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. ..
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    ..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. ..
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    ..02, both). ANGPTL4 is produced by human myotubes in response to LCFA via PPAR-delta, and muscle-derived ANGPTL4 seems to be of systemic relevance in humans. ..
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    ..In this study, we demonstrated that the induction of conformational change and transactivity of PPAR delta by arachidonic acid, as well as other polyunsaturated fatty acids, was considerably lower than that of PPAR ..
  75. Odegaard J, Ricardo Gonzalez R, Red Eagle A, Vats D, Morel C, Goforth M, et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab. 2008;7:496-507 pubmed publisher
    ..Taken together, these data suggest an unexpected beneficial role for alternatively activated Kupffer cells in metabolic syndrome and type 2 diabetes. ..
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    ..Taken together, the enhanced transcription of antioxidant genes is responsible for the PPAR?-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II. ..