Peroxisome proliferator-activated receptor gamma
Available structures
PDB Ortholog search: RCSB
RNA expression pattern

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor that in humans is encoded by the PPARG gene.[2][3][4]

Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine).[5]


PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice fail to generate adipose tissue when fed a high-fat diet.[6]

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Alternatively spliced transcript variants that encode different isoforms have been described.[7]


Peroxisome proliferator-activated receptor gamma has been shown to interact with:

Clinical relevance

PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia.[18] PPAR-gamma decreases the inflammatory response of many cardiovascular cells, particularly endothelial cells.[19] PPAR-gamma activates the PON1 gene, increasing synthesis and release of paraoxonase 1 from the liver, reducing atherosclerosis.[20]

Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes target PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. Different classes of compounds which activate PPARgamma weaker than thiazolidinediones (the so called “partial agonists of PPARgamma”) are currently studied with the hope that such compounds would be still effective hypoglycaemic agents but with fewer side effects.[21][22]

A fusion protein of PPAR-γ1 and the thyroid transcription factor PAX8 is present in approximately one-third of follicular thyroid carcinomas, to be specific those cancers with a chromosomal translocation of t(2;3)(q13;p25), which permits juxtaposition of portions of both genes.[23] [24]

Recently pioglitazone, a PPAR-γ agonist has been shown to be effective in reducing inflammation in Parkinson's Disease models. Levels of MMPs and microglia (and therefore TNF-α and other cytokine levels) were found to be reduced. Thus it has been shown to be neuroprotective in MPTP mouse models.


Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.