Peroxisome proliferator Sample Clauses

Peroxisome proliferator activated receptor γ The peroxisome-proliferator activated receptors (PPARs) are transcriptional regulators of cellular differentiation, development and lipid metabolism, activated by unsaturated fatty acids (Xxxxxxx & Xxxxxxxx, 2002). One of the most studied isoforms of the PPAR family is PPARγ. It is a transcription factor that is a member of the nuclear hormone receptor superfamily (Xxxxxx & Xxxxx, 2005), which has been of particular interest because of its dominant role in the control of the expression of genes related to inflammation, adipose cell differentiation, atherosclerosis, metabolism and cancer (Xxxxx et al, 2010). PPARγ controls biological functions by controlling the expression of specific genes, mainly in a ligand-dependant manner (Xxxxxx & Xxxxx, 2005). Ligands occur either naturally or in synthetic form. Natural ligands include linolenic, EPA, DHA and AA, as well as prostaglandin (Xu et al, 1999). The synthetic ligands include TZD, non-steroid and anti-inflammatory drugs (Xxxxxx & Xxxxx, 2005).

Peroxisome proliferator activated receptor α PPARα is another member of the group of nuclear receptors that regulate key proteins involved in inflammation, fatty acid oxidation, lipoprotein metabolism (Xxxxxx & Xxxxxx, 2010), extracellular lipid metabolism and haemostasis (Xxxx, 2009). It is mostly expressed in tissues with high levels of fatty acid oxidation, such as liver and muscle (Auboeuf et al, 1997), and it regulates target genes involved in the transportation and oxidation of fatty acids (Xxxxxx et al, 1998). The cytochrome P450 system, which is induced to metabolise foreign compounds including some lipids, is capable of producing PPARα ligands (Ng et al, 2007). PPARα ligands include exogenous lipid-lowering drugs such as clofibrate, fenofibrate and endogenous fatty acids, which include branched chain saturated (such as phytanic acid) and C20-22 unsaturated fatty acids (such as erucic acid 22:1n-9) (Xxxx, 2009; Xxxxxx et al, 2000). In the case of erucic acid, peroxysomes are induced to enable the microsomal chain shortening of erucic acid to 18:1 so that it can form carnitine esters and be translocated into the mitochondria for beta-oxidation (Xxxxxx et al, 1982). Like PPARγ, ligand-activated PPARα heterodimerises with RXR-α before binding to target gene promoters (Xxxxxxxxx et al, 2008), which usually contain one or more PPREs (Xxx et al, 1995). In addition, PPARα transactivation is modulated by cofactors or corepressors (Xxxx, 2009), which in the absence of a ligand inhibit its activity (Xxxxx et al, 2010). Studies have also found that PPARα can modulate its own expression (Xxxxxx et al, 2000; Xxxxx et al, 2010; Xxxxxx et al, 2002) and transcriptional activity is also regulated by phosphorylation, which stabilizes its binding to the PPRE (Xxxx, 2009). Studies in mice have shown that PPARα deficiency results in late-onset obesity (Xxxxxx et al, 1998) and the disruption of lipid metabolism (Xxxxxxx et al, 1998).