Fatty Acid Desaturation and the Regulation of Adiposity in Caenorhabditis elegans

Abstract

Abstract Monounsaturated fatty acids are essential components of membrane and storage lipids. Their synthesis depends on the conversion of saturated fatty acids to unsaturated fatty acids by Δ9 desaturases. Caenorhabditis elegans has three Δ9 desaturases encoded by the genes fat-5, fat-6, and fat-7. We generated nematodes that display a range of altered fatty acid compositions by constructing double-mutant strains that combine mutations in fat-5, fat-6, and fat-7. All three double-mutant combinations have reduced survival at low temperatures. The fat-5;fat-6 double mutants display relatively subtle fatty acid composition alterations under standard conditions, but extreme fatty acid composition changes and reduced survival in the absence of food. The strain with the most severe defect in the production of unsaturated fatty acids, fat-6;fat-7, exhibits slow growth and reduced fertility. Strikingly, the fat-6;fat-7 double-mutant animals have decreased fat stores and increased expression of genes involved in fatty acid oxidation. We conclude that the Δ9 desaturases, in addition to synthesizing unsaturated fatty acids for properly functioning membranes, play key roles in lipid partitioning and in the regulation of fat storage.