Arachidonic acid PPAR ligand

The principal LCPUFA of oo-6 series is arachidonic acid (AA 20 4) acting as a precursor for eicosanoids synthesized from LA. LCPUFAs of 00-6 series have been considered as activators of PPAR-y. Their metabolic effects include increased synthesis of cholesterol, increased activity of LDL receptors, increased activity of cholesterol 7 a-hydroxylase (Cyp 7A1), and decreased conversion of VLDL to LDL. As ligands of PPAR-y, co-6 PUFAs may improve insulin sensitivity, change fat distribution, and affect adipocyte differentiation (Chiang et ah, 2001 Corton and Anderson, 2000). 

Fig. 12. Panel A Inhibitory effects of various polyunsaturated fatty acids (PUFA) on sterol regulatory element binding protein (SREBP)-lc promoter activity. EtOH, ethanol SA, saturated fatty acid OL, oleic acid LA, linoleic acid DHA, docosa-hexaenoic acid EPA, eicosapentaenoic acid AA, arachidonic acid. Panel B Mechanism by which polyunsaturated fatty acids suppress the SREBP-1 c promoter activity, through an effect on the liver X receptor (LXR)/9-c/s-retinoic acid receptor (RXR) activation pathway [redrawn from Yoshikawa etal. (129), reproduced with permission]. PUFA competitively interfere with binding of the endogenous ligand (possibly oxysterols) to LXR, thereby repressing LXR/RXR transactivity and SREBP-lc and lipogenic gene expression. Meanwhile, PUFA can bind and activate peroxisome proliferator activated receptor-a (PPARa) to induce 3-oxidation of fatty acids. PPRE PPAR response element LXRE LXR response element.

Peroxisomes are intracellular cytoplasmic organelles and the major sites for enzymatic oxidation, including that of fatty acids. The proliferation of peroxisomes is stimulated by free fatty acids and some metabolites of arachidonic acid, which are ligands for nuclear receptor proteins, the PPARs. These, in turn, are a family of... 

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