Liu, Yasmine J.Gao, Arwen W.Smith, Reuben L.Janssens, Georges E.Panneman, Daan M.Jongejan, Aldovan Weeghel, MichelVaz, Frederic M.Silvestrini, Melissa J.Lapierre, Louis R.MacInnes, Alyson W.Houtkooper, Riekelt H.2022-03-282022-03-282022-03-282022-03-0110.1038/s41598-022-07397-9https://infoscience.epfl.ch/handle/20.500.14299/186680WOS:000763010000078Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans, while a basal expression of ech-6 was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat in ech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction between ech-6 and fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipase lipl-4 recapitulated the lifespan effects of fat diets on ech-6-silenced worms. Collectively, these results suggest that the gene ech-6 is potential modulator of metabolic flexibility and may be a target for promoting metabolic health and longevity.Multidisciplinary SciencesScience & Technology - Other Topicssystematic rnai screencaenorhabditis-eleganslipid-metabolismlongevitygenerestrictionintegrationextensionnetworksmdt-15text::journal::journal article::research article