genetic regulation of unsaturated fatty acid composition in c. elegans在秀丽隐杆线虫基因调节不饱和脂肪酸成分.pdfVIP

Genetic Regulation of Unsaturated Fatty Acid Composition in C. elegans * Trisha J. Brock, John Browse, Jennifer L. Watts Institute of Biological Chemistry, Washington State University, Pullman, Washington, United States of America Delta-9 desaturases, also known as stearoyl-CoA desaturases, are lipogenic enzymes responsible for the generation of vital components of membranes and energy storage molecules. We have identified a novel nuclear hormone receptor, NHR-80, that regulates delta-9 desaturase gene expression in Caenorhabditis elegans. Here we describe fatty acid compositions, lifespans, and gene expression studies of strains carrying mutations in nhr-80 and in the three genes encoding delta-9 desaturases, fat-5, fat-6, and fat-7. The delta-9 desaturase single mutants display only subtle changes in fatty acid composition and no other visible phenotypes, yet the fat-5;fat-6;fat-7 triple mutant is lethal, revealing that endogenous production of monounsaturated fatty acids is essential for survival. In the absence of FAT-6 or FAT-7, the expression of the remaining desaturases increases, and this ability to compensate depends on NHR-80. We conclude that, like mammals, C. elegans requires adequate synthesis of unsaturated fatty acids and maintains complex regulation of the delta-9 desaturases to achieve optimal fatty acid composition. Citation: Brock TJ, Browse J, Watts JL (2006) Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2(7): e108. DOI: 10.1371/journal.pgen.0020108 Introduction (PPARa) have been identified as key transcriptional regu- lators of SCD1 gene expression in mammals [5]. The SREBP-1 Monounsaturated fatty acids (MUFAs) are