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• W1968798976 startingPage "724" @default.
• W1968798976 abstract "Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects against the cellular inflammatory response, and is central to fatty acid-mediated upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha activators may likewise up-regulate mHS expression in brain. Thus, to attempt pharmacological activation of brain PPAR alpha in vivo, we have administered to rats two drugs with previously defined actions in rat brain, namely the PPAR alpha-selective activator ciprofibrate and the pan-PPAR activator valproate. Using the sensitive and discriminatory RNase protection co-assay, we demonstrate that both ciprofibrate and valproate induce mHS expression in liver, the archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently increases mHS mRNA abundance in rat brain, together with lesser increases in two other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up-regulation of expression of PPAR alpha-dependent genes including mHS in brain, with implications in the increased elimination of neuro-inflammatory lipids and concomitant increased production of neuro-protective ketone bodies." @default.
• W1968798976 created "2016-06-24" @default.
• W1968798976 creator A5019755982 @default.
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• W1968798976 date "2002-04-01" @default.
• W1968798976 modified "2023-09-25" @default.
• W1968798976 title "The peroxisome proliferator-activated receptor α-selective activator ciprofibrate upregulates expression of genes encoding fatty acid oxidation and ketogenesis enzymes in rat brain" @default.
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• W1968798976 doi "https://doi.org/10.1016/s0028-3908(02)00014-x" @default.
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