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bioRxiv · 10.1101/2024.10.01.616130

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

Battista, B.·Hernandez-Cravero, B.·Colaiacovo, M. P.·Cochella, L.·Binolfi, A.·de Mendoza, D.
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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 ({Delta}9) desaturases. In C. elegans, three {Delta}9 desaturases are encoded by the genes fat-5, fat-6, and fat-7. The presence of multiple {Delta}9 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 L1 and L2 stage. 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. SummaryUnsaturated fatty acids (UFAs) are essential for life. In animals, UFAs are synthesized by {Delta}9 desaturase enzymes. Caenorhabditis elegans possesses three {Delta}9 desaturase genes: fat-5, fat-6, and fat-7. We engineered a strain where fat-7 can be reversibly switched off while fat-5 and fat-6 are deleted, allowing precise control of UFA levels throughout the life cycle. Our findings demonstrate the critical role of UFA biosynthesis in early development and its direct link to fat storage and lipid turnover. This strain enables the study of UFA-related physiological and pathological processes in animals.

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Battista, B., Hernandez-Cravero, B., Colaiacovo, M. P., Cochella, L., Binolfi, A., de Mendoza, D.. 2024-10-03. An inducible and reversible system to regulate unsaturated fatty acid biosynthesis in C. elegans. https://doi.org/10.1101/2024.10.01.616130

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