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A more recent version of this article appeared on April 1, 2005

Papers In Press, published online ahead of print January 16, 2005
J. Lipid Res., doi:10.1194/jlr.M400335-JLR200
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Submitted on September 3, 2004
Revised on January 5, 2005
Accepted on January 11, 2005

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

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

Physiology, Michigan State University, East Lansing, MI 48824

Corresponding Author: jump{at}msu.edu

Although the physiological significance of microsomal fatty acid elongation is well-recognized, the regulation of fatty acid elongase expression remains poorly defined. Of the 6 elongase subtypes expressed in mammals, adult rat liver expresses 4 elongase subtypes; Elovl-5 > Elovl-1 = Elovl-2 = Elovl-6. Nutritional and developmental regulation of hepatic fatty acid elongase activity, as well as the expression of 4 elongases (Elovl-1, Elovl-2, Elovl-5 and Elovl-6), 3 fatty acid desaturases (delta 5, delta 6 and delta 9) and fatty acid synthase (FAS) was examined. Overnight starvation and fish oil enriched diets repressed hepatic elongase activity in adult male rats. Nutritional regulation of hepatic fatty acid elongase activity correlated with Elovl-5 and Elovl-6 mRNA abundance. Adult rats fed the PPAR-alpha agonist, WY14,643, have elevated hepatic elongase activity, Elovl-1, Elovl-5, Elovl-6, delta 5, delta 6 & delta 9 desaturase mRNA abundance, and 20:3,n-9 in both liver and plasma. 20:3n9 is a product of 18:1,n-9 elongation and desaturation. Thus, PPAR-alpha agonists impact both fatty acid elongation and desaturation pathways. Hepatic fatty acid elongase activity is low in fetal liver, but increased significantly after birth. Developmental changes in hepatic elongase activity parallel changes in Elovl-5 mRNA abundance, along with the PPARalpha-regulated transcripts, delta 5 and delta 6 desaturase and CYP4A. In contrast, Elovl-6, delta 9 desaturase and FAS mRNA abundance paralleled changes in hepatic SREBP-1c nuclear content. SREBP-1c is present in fetal liver nuclei, absent from nuclei immediately after birth and reappeared in nuclei at weaning, 21 days postpartum. In conclusion, Elovl-5 mRNA is the most abundant elongase subtype expressed in rat liver. Hepatic Elovl-5, delta 5 and delta 6 desaturase are coordinately regulated by diet and during postnatal development. Changes in Elovl-5 expression may account for much of the nutrition and developmental control of fatty acid elongation activity in the rat liver.


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