An inducible and reversible system to regulate unsaturated fatty acid biosynthesis in C. elegans

Abstract

Unsaturated fatty acids (UFAs) play crucial roles in various physiological and pathological processes. In animals, these lipids are synthesized from saturated fatty acids through the action of delta 9 (Δ9) desaturases. In C. elegans, three Δ9 desaturases are encoded by the genes fat-5, fat-6, and fat-7. The presence of multiple Δ9 desaturases has posed a significant challenge in developing a rapid and efficient approach to control UFA production in C. elegans and other model organisms. Utilizing the auxin-inducible degradation system, we specifically targeted the C. elegans fat-7 gene, responsible for the major stearoyl-CoA desaturase (SCD), while deleting fat-5 and fat-6. This design resulted in a strain that can be reversibly depleted of UFAs in the cells of interest. Conditional depletion in all somatic cells exhibited a pronounced auxin-dependent defect in UFA production. Using this system, we uncovered an essential requirement for de novo UFA production during the L1 and L2 stages. Moreover, our results support a direct connection between UFA levels, fat storage, and increased lipid turnover. This system will enable further studies exploring the cellular and physiological consequences of impairing UFA biosynthesis at different developmental stages or in specific tissues.

Keywords: C. elegans; AID system; cold stress; fertility; inducible depletion of UFA; lipid droplets; lipid storage; solution-state NMR spectroscopy.