PPARD (peroxisome proliferator-activated receptor delta)

2009-06-01   Erhan Astarci , Sreeparna Banerjee 

Department of Biology, Middle East Technical University, Ankara 06531, Turkey





PPAR delta gene is located on chromosome 6p21-22.
Atlas Image
PPAR delta gene diagram. Red boxes indicate the exons. Start and stop codons are shown by the two arrows respectively.


According to Entrez-Gene, PPARD gene maps to NC_000006.10 and spans a region of 10.7 kilo bases. According to Spidey (mRNA to genomic sequence alignment tool), PPAR delta has 8 exons, the sizes being 124, 84, 231, 155, 139, 203, 451, 2347.


PPAR delta mRNA NM_006238 has 3734 bp.
PPAR-delta is activated by either hypolipidemic drugs or fatty acids. The mammalian counterparts are particularly activated by 18C unsaturated fatty acids.
According to GeneCards, PPAR delta expression was detected in 12 human tissues including spleen, thymus, brain, spinal cord, heart, skeletal cord, liver, pancreas, prostate, kidney and lung.


According to Entrez Gene, ppar delta (PPARD) has no known pseudogenes.



PPARD has two protein isoforms produced by alternative splicing. PPAR delta acts as a transcription factor in the presence of a ligand and after heterodimerization with the retinoid acid X receptor.


PPARD protein is composed of 441 amino acids and has a molecular weight of 49.9 kDa. According to the NCBI conserved domain search, the protein contains two zinc finger C4 type domains which is a conserved domain in proteins with DNA binding activity. The protein also has a flexible hinge region and a ligand binding domain near the C terminus.


PPAR delta is expressed in wide range of tissues and is highly expressed in spleen, thymus, brain, spinal cord, heart, skeletal cord, liver, pancreas, prostate, kidney and lung.


Located in the nucleus.


Similar to other peroxisome proliferator activated receptors PPAR delta is also involved in differentiation and metabolism. Fatty acid regulation and oxidation in skeletal muscle and adipose tissues is one of the major functions of PPAR delta. It has been shown that the increase in muscle oxidative capacity correlates positively with PPAR delta expression. Additionally, fatty acid efflux is also regulated by PPAR delta by redirection of the fatty acid ligand from the adipose tissue to the skeletal muscles which results in a decrease in the size of the adipose tissue. Fatty acids are natural ligands of the PPAR delta and it is known that its activity increases by certain eicosanoids like leukotriene B4.


Canis familiaris: PPAR-beta, peroxisome proliferator-activated receptor delta.
Pan troglodytes: LOC463188, peroxisome proliferator-activated receptor delta.
Rattus norvegicus: Ppard, peroxisome proliferator activated receptor delta.
Mus musculus: Ppard, peroxisome proliferator activator receptor delta.
Gallus gallus: PPARD, peroxisome proliferator-activated receptor delta.



SNP rs1053049 rs6902123 rs2267668 are associated with insulin resistance.
SNP rs2016520, rs3734254 and rs9794 are associated with obesity.
Gly482Ser is associated with insulin resistance.
-87T/C polymorphism is associated with alterations in cholesterol metabolism.
-13454G>T, c.2022+12G>A, c.2629T>C, c.2806C>G are associated with obesity.

Implicated in

Entity name
Colorectal cancer
PPARdelta is overexpressed in human colon cancers and genetic disruption of the gene in mice was shown to significantly reduce the incidence of colorectal cancer by reducing expression of vascular endothelial growth factor. Additionally, Wnt/beta-catenin has been shown to stimulate PPAR delta expression. Activation of the COX-2 pathway resulting in the production of prostaglandin E2 activated PPAR delta via the PI3K-Akt pathway. PPAR delta can also cross talk with other transcription factors such as nuclear factor kappa B. PPAR delta is highly expressed in the gastrointestinal tract in a constitutive manner where it regulates cell proliferation and differentiation. In mouse it has been shown that mouse PPAR delta has both ligand dependent and independent effects and ligand independent effects are involved in down regulation of inflammation whereas the ligand dependent effects include proliferation and differentiation. Contradicting results support that PPARdelta can induce or alleviate the disease progression.
Entity name
Insulin resistance
Single nucleotide polymorphisms (SNPs) in the PPAR delta gene are associated with insulin resistance and increased fat storage due to an interference in mitochondrial functions. After having genotyped 156 patients for the reference SNPs (rs) who are in the risk group for type 2 diabetes, they were shown to carry the SNPs rs1053049, rs6902123, and rs2267668 (A:A, A:G, A:G respectively) in the PPAR delta gene.
Another study indicated that a (-87 T/C) polymorphism affects both plasma glucose levels in the fasting state, insulin sensitivity and cholesterol metabolism. Carriers with the C allele displayed increased plasma glucose levels and decreased insulin sensitivity with respect to the T allele carrying counterparts. Higher titer of low density lipoprotein was also observed in the C allele carriers. It was also concluded that higher levels of fasting plasma glucose levels were independent from the etiology of being diabetic or glucose tolerant. In both cases, insulin sensitivity was disrupted.
Entity name
Catabolism of fats has been shown to be regulated by PPAR delta which could thus be exploited as a potential target for the treatment of obesity and type-2 diabetes. Of the nine polymorphic markers sequenced in the PPAR delta gene four polymorphisms were found in the intronic regions, one in an untranslated region and four in the 3 untranslated region (UTR). The polymorphisms were -13454G>T, c.-87T>C, c.2022+12G>A, c.2629T>C, and c.2806C>G. The same polymorphisms, however, were not significantly associated with the risk for Type 2 diabetes. However in terms of fasting plasma glucose levels and body mass index, the findings were found to be associated with obesity.
Entity name
As lipid metabolism is involved in atherogenesis, the effects PPARdelta expression in atherosclerotic changes in macrophages were investigated. It has been shown that use of PPAR delta agonists reduces atherosclerosis in apoE double negative mice. The mechanism has been shown to be through elevation of high density lipoprotein level and suppression of inflammation possibly by the down regulation of chemokines which then results in a decrease in the chemoattractant signaling. PPARdelta activation is also associated with the increased expression of G-protein signaling genes which has been shown to block the chemokine receptors.


Pubmed IDLast YearTitleAuthors
183375092008PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis.Barish GD et al
151280522004Effects of PPARalpha, gamma and delta haplotypes on plasma levels of lipids, severity and progression of coronary atherosclerosis and response to statin therapy in the lipoprotein coronary atherosclerosis study.Chen S et al
194340502009PPARs: the vasculature, inflammation and hypertension.Duan SZ et al
184424722008Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice.Girroir EE et al
171161802006Peroxisome proliferator-activated receptor (PPAR) delta genetic polymorphism and its association with insulin resistance index and fasting plasma glucose concentrations in Chinese subjects.Hu C et al
165564932006Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer.Jiang WG et al
184656552008PPARbeta/delta ligands as modulators of the inflammatory response.Kilgore KS et al
166187652006Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis.Marin HE et al
161412402006NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)delta expression in APC(min/+) mice proportionally to their tumor inhibitory effect: Implications for the role of PPARdelta in carcinogenesis.Ouyang N et al
186164312008Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease.Peters JM et al
193897992009Activation of PPARbeta/delta inhibits leukocyte recruitment, cell adhesion molecule expression, and chemokine release.Piqueras L et al
149882732004Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.Shin HD et al
173273852007Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention.Stefan N et al
182527922008Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study.Thamer C et al
184792612008A gut feeling of the PXR, PPAR and NF-kappaB connection.Wahli W et al
186151832008The PPAR-gamma Agonist 15-Deoxy-Delta-Prostaglandin J(2) Attenuates Microglial Production of IL-12 Family Cytokines: Potential Relevance to Alzheimer's Disease.Xu J et al
194360362009Targeted genetic disruption of peroxisome proliferator-activated receptor-delta and colonic tumorigenesis.Zuo X et al

Other Information

Locus ID:

NCBI: 5467
MIM: 600409
HGNC: 9235
Ensembl: ENSG00000112033


dbSNP: 5467
ClinVar: 5467
TCGA: ENSG00000112033


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
PPAR signaling pathwayKEGGko03320
Wnt signaling pathwayKEGGko04310
Acute myeloid leukemiaKEGGko05221
PPAR signaling pathwayKEGGhsa03320
Wnt signaling pathwayKEGGhsa04310
Pathways in cancerKEGGhsa05200
Acute myeloid leukemiaKEGGhsa05221
Signal TransductionREACTOMER-HSA-162582
Signaling by Retinoic AcidREACTOMER-HSA-5362517
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Nuclear Receptor transcription pathwayREACTOMER-HSA-383280
Metabolism of lipids and lipoproteinsREACTOMER-HSA-556833
Fatty acid, triacylglycerol, and ketone body metabolismREACTOMER-HSA-535734
Import of palmitoyl-CoA into the mitochondrial matrixREACTOMER-HSA-200425
The citric acid (TCA) cycle and respiratory electron transportREACTOMER-HSA-1428517
Pyruvate metabolism and Citric Acid (TCA) cycleREACTOMER-HSA-71406
Pyruvate metabolismREACTOMER-HSA-70268
Regulation of pyruvate dehydrogenase (PDH) complexREACTOMER-HSA-204174

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA445425Prostatic NeoplasmsDiseaseClinicalAnnotationassociatedPD20038957


Pubmed IDYearTitleCitations
165115912006PPAR delta: a dagger in the heart of the metabolic syndrome.179
198382022009PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance.130
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
147583562004Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth.84
180248532008Activation 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.83
171486042006Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.81
170682882007Activation of PPARbeta/delta induces endothelial cell proliferation and angiogenesis.78
129097232003The 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid down-regulates PPAR-delta to induce apoptosis in colorectal cancer cells.73
181826822008Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology.71
190749892009Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator-activated receptor (PPAR)-delta and is of metabolic relevance in humans.70


Erhan Astarci ; Sreeparna Banerjee

PPARD (peroxisome proliferator-activated receptor delta)

Atlas Genet Cytogenet Oncol Haematol. 2009-06-01

Online version: http://atlasgeneticsoncology.org/gene/41794/ppard-(peroxisome-proliferator-activated-receptor-delta)