The peroxisome proliferator-activated receptor (PPAR) family are ligand-activated nuclear transcription factors involved in the regulation of lipid metabolism through gene expression of peroxisome number. It is thought that the PPAR are activated by C18 to C22 n-3 and n-6 fatty acids, which in turn increases gene expression of peroxisomes, which then increases cellular oxidation of medium and long chain fatty acids. The falmily comprises of a number of isoforms present in different tissues that can be categorised into PPARα, PPARβ (also called PPARδ) and PPARγ. The PPARγ receptor is then further split into PPARγ1, PPARγ2, and the PPARγ3 receptors. As well as their ability to regulate fatty acid oxidation, the PPAR family of receptors has been shown to be involved in cell proliferation, cell differentiation and the inflammatory response. Polyunsaturated fatty acids and their eicosanoid metabolites may therefore provide protection from cancers via activation of the PPAR family of receptors.
For example, PPARα is activated by palmitic acid (PA, C16:0), oleic acid (OA, C18:1 (n-9)), linoleic acid (LA, C18:2 (n-6)), docosahexanoic acid (DHA, C22:5 (n-3)) and α-linolenic acid (ALA, C18 (n-3)). Similarly, the PPARγ receptor is activated by eicosapentanoic acid (EPA, C20:5 (n-3)), LA, ALA and arachidonic acid (AA, C20:4 (n-3)), and eicosanoids such as PGJ2 and 15-hydroxyeicosatraenoic acid (15-HETE). Activation of the PPARγ receptor has ant proliferative effects both in vivo and in vitro and both PPARα and PPARγ have been shown to have anti-inflammatory effects in vitro. The PPARβ receptor is activated by dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)), EPA, AA, palmitic acid (PA, C16:0) and prostaglandin PGA1 and PGD3. Activation of PPARβ may also play a role in cell proliferation but its role is not understood. The specificity of different isoforms of PPAR to different fatty acids suggests that dietary ratios of fatty acids may be important in the prevention of cancers, as has been evidenced in epidemiological studies.
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