Peroxisome proliferator-activated receptor polyunsaturated fatty acids

Forman, B. M., Chen, J., and Evans, R. M. (1997). Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc. Natl. Acad. Sci. USA 94, 4312-4317. 

Ren, B., Thelen, A. P., Peters, J. M., Gonzalez, F. J., and Jump, D. B. Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha. J Biol Chem 272 (1997) 26827-26832. 

Abbreviations AA arachidonic acid AFA alpha-linolenic acid AP-1 activator protein 1 COX cyclooxygenase DFIA docosahexaenoic acid EPA eicosapentaenoic acid IF interleukin FA linoleic acid FOX lipoxygenase EPS lipopolysaccaride FT leukotriene NF-kB nuclear factor-kappa B, PG prostaglandin PPARs peroxisome proliferator-activated receptors PUFA polyunsaturated fatty acids, RvEl resolvin El, TNFa tumor necrosis factor alpha, TX thromboxane... 

Fig. 6. Coordinated transcriptional regulation of fatty acid desaturases and elongases in mammals. PUFA, polyunsaturated fatty acids +, stimulation inhibition LXR, liver X receptor RXR retinoid X receptor SREBP, sterol regulatory element binding protein ChREBP, carbohydrate response element binding protein Mix, Max-like receptor PPAR-ot, peroxisome proliferator activated receptor alpha LXRE, liver X receptor response element SRE, sterol response element ChoRE, carbohydrate response element PPRE, peroxisome proliferator response element. (See color plate section, plate no. 6.)...

Moreover, studies about lipidogenesis and lipid metabolism have focused on a nuclear receptor, peroxisome proliferation-activated receptor y (PPAR-y). PPAR-y gene is a good example for involvement in a gene-environment interaction. Activation of PPAR-y leads to peroxisome proliferation and increased oxidation of fatty acids. PPAR-y activation results in adipocyte differentiation as well as improved insulin signaling of mature adipocytes. PPAR-y is associated with insulin resistance and blood pressure [5]. In individuals with a specific polymorphism in the PPAR-y (Prol2Ala), a low polyunsaturated-to-saturated fat ratio has been demonstrated to be associated with an increase in body mass index and fasting insulin concentrations [88]. 

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.

Hepatic S14 Gene Transcription. Evidence Against the Peroxisome Proliferator-Activated Receptor a as the Mediator of Polyunsaturated Fatty Acid Regulation of sl4 Gene Transcription.277 17167—17173 (1996). 

Abbreviations a-BFAs anteiso-branched fatty acids AGP acyl carrier protein BHLH active soluble domain of SREBP CNS central nervous system DSD delta 5 desaturase D6D delta 6 desaturase ER endoplasmic reticulum Hik histidine kinase HUFA highly unsaturated fatty acid LXR liver X receptor MUFA monounsaturated fatty add NF-Y nuclear factor Y PLs phospholipids PP peroxisome proliferator PPAR PP-activated receptor PPRE PP response element PUFA polyunsaturated fatty acid PUFA-BP PUFA binding protein PUFA-RE PUFA response element RXR retinoid X receptor SCAP SREBP cleavage-activating protein SCD steraroyl CoA desaturase SFA saturated fatty acid SRE sterol response... 

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