@article{12ccdd5b0d954efa84a991ca62aeb8dd,
title = "Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans",
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 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.",
keywords = "Aging/genetics, Animals, Caenorhabditis elegans Proteins/genetics, Caenorhabditis elegans/metabolism, Longevity/genetics, Lysosomes/metabolism",
author = "Liu, {Yasmine J.} and Gao, {Arwen W.} and Smith, {Reuben L.} and Janssens, {Georges E.} and Panneman, {Daan M.} and Aldo Jongejan and {van Weeghel}, Michel and Vaz, {Fr{\'e}d{\'e}ric M.} and Silvestrini, {Melissa J.} and Lapierre, {Louis R.} and MacInnes, {Alyson W.} and Houtkooper, {Riekelt H.}",
note = "Funding Information: Work in the Houtkooper group is financially supported by an ERC Starting grant (no. 638290), and a VIDI grant from ZonMw (no. 91715305), and a grant from the Velux Stiftung (no. 1063). A.W.G. was supported by an AMC PhD Scholarship. A.W.M. is supported by E-Rare-2, the ERA-Net for Research on Rare Diseases (ZonMW #40-44000-98-1008). G.E.J. is supported by a Federation of European Biochemical Society (FEBS, https://www.febs.org ) long-term fellowship and a VENI Grant from ZonMw (no. 09150161810014, https://www.zonmw.nl ). L.R.L. is funded by an R00 (AG042494) and an R01 (AG051810) from the National Institute of Health. The authors thank the Caenorhabditis Genetics Center at the University of Minnesota for providing C. elegans strains. The authors also thank Lodewijk IJlst and Simone W. Denis for advice on the manuscript. Funding Information: Work in the Houtkooper group is financially supported by an ERC Starting grant (no. 638290), and a VIDI grant from ZonMw (no. 91715305), and a grant from the Velux Stiftung (no. 1063). A.W.G. was supported by an AMC PhD Scholarship. A.W.M. is supported by E-Rare-2, the ERA-Net for Research on Rare Diseases (ZonMW #40-44000-98-1008). G.E.J. is supported by a Federation of European Biochemical Society (FEBS, https://www.febs.org) long-term fellowship and a VENI Grant from ZonMw (no. 09150161810014, https://www.zonmw.nl). L.R.L. is funded by an R00 (AG042494) and an R01 (AG051810) from the National Institute of Health. The authors thank the Caenorhabditis Genetics Center at the University of Minnesota for providing C. elegans strains. The authors also thank Lodewijk IJlst and Simone W. Denis for advice on the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "https://doi.org/10.1038/s41598-022-07397-9",
language = "English",
volume = "12",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Springer Nature",
number = "1",
}