Peroxisome Proliferator-Activated Receptor Gamma (abbreviated to PPARG or less commonly PPAR-γ) is a nuclear receptor. It is known by a number of other names too, such as the glitazone receptor, or NR1C3 (Nuclear Receptor Subfamily 1, Group C, Member 3). It is a type II nuclear receptor which is encoded by the PPARG gene in human physiology.
PPARG is mostly present in adipose tissues- tissues which store energy in the form of fat such as those found in the colon and macrophages. Two isoforms of PPARG have been detected in humans and in studies with mice. These are PPAR-γ1 (which is found in most tissues in the body except for muscle tissues) and PPAR-γ2 (predominantly found in adipose and intestinal tissue).
PPARG Mechanism and Function
PPARG regulates the storage of fatty acids and the metabolism of glucose. The genes activated by PPARG stimulate adipogenesis and lipid uptake in fat cells. PPARG knockout mice which were fed a high-fat diet were unable to generate adipose tissue.
PPRG is a member of the Peroxisome Proliferator-Activated Receptor (PPAR) subfamily of nuclear receptors. These PPARs form heterodimers with retinoid X receptors (RXRs) which in turn are crucial in regulating the transcription of numerous different genes.
Currently there are three known subtypes of PPARs: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-Gamma which regulates adipocyte differentiation.
PPARG binds directly with a wide array of naturally occurring agents. These include arachidonic acid and various other polyunsaturated fatty acids. It also binds with arachidonic acid metabolites including some members of the 5-hydroxyicosatetraenoicacid and 5-oxo-eicosatetraenoic acid family.
These include the phytocannabinoid tetrahydrocannabinol (THC), the component responsible for the psychotropic effects of the cannabis plant, as well as its metabolite THC-COOH, and its synthetic analog ajulemic acid (AJA).
PPARG activation via these and other ligands may be responsible for inhibiting the growth of cultured cancer cell lines in cultured human tissues including those of the lung, prostate, breast, and stomach.
PPRG has a wide range of implications for the pathology of diseases from cancer and diabetes to atherosclerosis and obesity. PPAR-gamma agonists have also been used in the treatment of hyperglycemia and hyperlipidemia.
What makes OORG such a potent tool in the study of medicine is its anti-inflammatory properties. It decreases the inflammatory response of numerous cardiovascular cells, especially endothelial cells which line the blood and lymphatic vessels.
PPRG also activates the PON1 gene to encourage the synthesis release of paraoxonase 1 from the liver to help reduce atherosclerosis. PPARG activation is also potentially useful in the treatment of diabetes with numerous insulin sensitizing drugs using it to lower serum glucose without increasing pancreatic insulin secretion.
However, it has been noted that the activation of PPARG has proven more effective for skeletal and muscular insulin resistance than for insulin resistance of the liver. Different kinds of compounds have been experimented with for PPARG activation which are weaker than thiazolidinediones (PPARG’s partial agonists). These are currently studied in hopes of providing effective hypoglycemic agents with minimal side effects.