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  • 标题:Peroxisome proliferator-activated receptor {alpha} is required for feedback regulation of highly unsaturated fatty acid synthesis
  • 本地全文:下载
  • 作者:Li, Yue ; Nara, Takayuki Y. ; Nakamura, Manabu T.
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2005
  • 卷号:46
  • 期号:11
  • 页码:2432-2440
  • DOI:10.1194/jlr.M500237-JLR200
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:{Delta}6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction. Paradoxically, D6D is also induced by ligands of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}). Here, we report a novel physiological role of PPAR{alpha} in the induction of genes specific for HUFA synthesis by essential fatty acid-deficient diets. D6D mRNA induction by essential fatty acid-deficient diets in wild-type mice was diminished in PPAR{alpha}-null mice. This impaired D6D induction in PPAR{alpha}-null mice was not attributable to feedback suppression by tissue HUFAs because PPAR{alpha}-null mice had lower HUFAs in liver phospholipids than did wild-type mice. Furthermore, PPAR{alpha}-responsive genes were induced in wild-type mice under essential fatty acid deficiency, suggesting the generation of endogenous PPAR{alpha} ligand(s). Contrary to genes for HUFA synthesis, the induction of other lipogenic genes under essential fatty acid deficiency was higher in PPAR{alpha}-null mice than in wild-type mice even though mature SREBP-1c protein did not differ between the genotypes. The expression of PPAR{gamma} was markedly increased in PPAR{alpha}-null mice and might have contributed to the induction of genes for de novo lipogenesis. Our study suggests that PPAR{alpha}, together with SREBP-1c, senses HUFA status and confers pathway-specific induction of HUFA synthesis by essential fatty acid-deficient diets. Abbreviations: ACBP, acyl-coenzyme A binding protein; AOX, acyl-coenzyme A oxidase; CYP, cytochrome P450; D5D, {Delta}5 desaturase; D6D, {Delta}6 desaturase; HUFA, highly unsaturated fatty acid; PK, pyruvate kinase; PPAR, peroxisome proliferator-activated receptor; PPRE, peroxisome proliferator response element; SCD, stearoyl-coenzyme A desaturase; SREBP, sterol regulatory element-binding protein; TRB3, mammalian tribbles homolog Supplementary key words {Delta}6 desaturase • arachidonic acid • docosahexaenoic acid • essential fat deficiency • liver • peroxisome proliferator-activated receptor {alpha}-null mouse • polyunsaturated fatty acid • sterol regulatory element-binding protein-1c
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