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  • 标题:Peroxisome proliferator-activated receptor-α accelerates α-chlorofatty acid catabolism
  • 本地全文:下载
  • 作者:Elisa N. D. Palladino ; Wen-yi Wang ; Carolyn J. Albert
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2017
  • 卷号:58
  • 期号:2
  • 页码:317-324
  • DOI:10.1194/jlr.M069740
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:α-Chlorofatty aldehydes are generated from myeloperoxidase-derived HOCl targeting plasmalogens, and are subsequently oxidized to α-chlorofatty acids (α-ClFAs). The catabolic pathway for α-ClFA is initiated by ω-oxidation. Here, we examine PPAR-α activation as a mechanism to increase α-ClFA catabolism. Pretreating both HepG2 cells and primary mouse hepatocytes with the PPAR-α agonist, pirinixic acid (Wy 14643), increased the production of α-chlorodicarboxylic acids (α-ClDCAs) in cells treated with exogenous α-ClFA. Additionally, α-ClDCA production in Wy 14643-pretreated wild-type mouse hepatocytes was accompanied by a reduction in cellular free α-ClFA. The dependence of PPAR-α-accelerated α-ClFA catabolism was further demonstrated by both impaired metabolism in mouse PPAR-α−/− hepatocytes and decreased clearance of plasma α-ClFA in PPAR-α−/− mice. Furthermore, Wy 14643 treatments decreased plasma 2-chlorohexadecanoic acid levels in wild-type mice. Additional studies showed that α-ClFA increases PPAR-α, PPAR-δ, and PPAR-γ activities, as well as mRNA expression of the PPAR-α target genes, CD36, CPT1a, Cyp4a10, and CIDEC. Collectively, these results indicate that PPAR-α accelerates important pathways for the clearance of α-ClFA, and α-ClFA may, in part, accelerate its catabolism by serving as a ligand for PPAR-α.
  • 关键词:myeloperoxidase ; lipid biochemistry ; fatty acid ; fatty acid/oxidation ; liver metabolism ; nuclear receptors/peroxisome proliferator-activated receptor
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