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标题：Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases
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作者：Wang, Yun ; Botolin, Daniela ; Christian, Barbara 等
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：04
页码：706-715
DOI：10.1194/jlr.M400335-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Of the six fatty acid elongase (Elovl) subtypes expressed inmammals, adult rat liver expresses four subtypes: Elovl-5 >Elovl-1 = Elovl-2 = Elovl-6. Overnight starvation and fish oil-enricheddiets repressed hepatic elongase activity in livers of adultmale rats. Diet-induced changes in elongase activity correlatewith Elovl-5 and Elovl-6 mRNA abundance. Adult rats fed theperoxisome proliferator-activated receptor ${alpha}$ (PPAR ${alpha}$ ) agonist WY14,643have increased hepatic elongase activity, Elovl-1, Elovl-5,Elovl-6, ${Delta}$ ⁵, ${Delta}$ ⁶, and ${Delta}$ ⁹ desaturase mRNA abundance, and mead acid(20:3,n-9) content. PPAR ${alpha}$ agonists affect both fatty acid elongationand desaturation pathways leading to changes in hepatic lipidcomposition. Elovl activity is low in fetal liver but increasessignificantly after birth. Developmental changes in hepaticelongase activity paralleled the postnatal induction of Elovl-5mRNA and mRNAs encoding the PPAR ${alpha}$ -regulated transcripts, ${Delta}$ ⁵ and ${Delta}$ ⁶ desaturase, and cytochrome P450 4A. In contrast, Elovl-6, ${Delta}$ ⁹ desaturase, and FAS mRNA abundance paralleled changes in hepaticsterol regulatory element binding protein 1c (SREBP-1c) nuclearcontent. SREBP-1c is present in fetal liver nuclei, absent fromnuclei immediately after birth, and reappears in nuclei at weaning,21 days postpartum. In conclusion, changes in Elovl-5 expression may account formuch of the nutritional and developmental control of fatty acidelongation activity in the rat liver. Abbreviations: ChREBP, carbohydrate regulatory element binding protein; CYP, cytochrome P450; DNL, de novo lipogenesis; EFAD, essential fatty acid deficiency; Elovl, fatty acid elongase; HiCHO, high-carbohydrate; HNF, hepatic nuclear factor; LXR, liver X receptor ${alpha}$ ; MLX, MAX-like factor; PPAR, peroxisome proliferator-activated receptor; SREBP, sterol regulatory element binding protein Supplementary key words fatty acid desaturase • postnatal development • polyunsaturated fatty acids • peroxisome proliferator-activated receptor ${alpha}$ • sterol regulatory element binding protein-1c