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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M400335-JLR200 on January 16, 2005

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Journal of Lipid Research, Vol. 46, 706-715, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases

Yun Wang, Daniela Botolin, Barbara Christian, Julia Busik, Jinghua Xu and Donald B. Jump1

Departments of Physiology, Biochemistry, and Molecular Biology, Michigan State University, East Lansing, MI 48824

1 To whom correspondence should be addressed. e-mail: jump{at}msu.edu

Of the six fatty acid elongase (Elovl) subtypes expressed in mammals, adult rat liver expresses four subtypes: Elovl-5 > Elovl-1 = Elovl-2 = Elovl-6. Overnight starvation and fish oil-enriched diets repressed hepatic elongase activity in livers of adult male rats. Diet-induced changes in elongase activity correlate with Elovl-5 and Elovl-6 mRNA abundance. Adult rats fed the peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) agonist WY14,643 have 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 elongation and desaturation pathways leading to changes in hepatic lipid composition. Elovl activity is low in fetal liver but increases significantly after birth. Developmental changes in hepatic elongase activity paralleled the postnatal induction of Elovl-5 mRNA 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 hepatic sterol regulatory element binding protein 1c (SREBP-1c) nuclear content. SREBP-1c is present in fetal liver nuclei, absent from nuclei immediately after birth, and reappears in nuclei at weaning, 21 days postpartum.

In conclusion, changes in Elovl-5 expression may account for much of the nutritional and developmental control of fatty acid elongation 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


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