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bioRxiv · 10.1101/2020.11.02.364760

Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans

Liu, Y. J.·Gao, A. W.·Smith, R. L.·Janssens, G. E.·Panneman, D. M.·Jongejan, A.·van Weeghel, M.·Vaz, F. M.·Silvestrini, M. J.·Lapierre, L. R.·MacInnes, A. W.·Houtkooper, R. H.
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Abstract

Deregulated 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 high-fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipase lipl-4 recapitulated the lifespan effects of high-fat diets on ech-6-silenced worms. Collectively, these results reveal that the gene ech-6 modulates metabolic flexibility and may be a target for promoting metabolic health and longevity.

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Liu, Y. J., Gao, A. W., Smith, R. L., Janssens, G. E., Panneman, D. M., Jongejan, A., van Weeghel, M., Vaz, F. M., Silvestrini, M. J., Lapierre, L. R., MacInnes, A. W., Houtkooper, R. H.. 2020-11-02. Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans. https://doi.org/10.1101/2020.11.02.364760

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