Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging
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nihms958069.pdf
Description
Accepted version
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963.83 KB
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Author(s)
Mihaylova, Maria M.
Cheng, Chia-Wei
Cao, Amanda Q.
Tripathi, Surya
Mana, Miyeko D.
Bauer-Rowe, Khristian E.
Abu-Remaileh, Monther
Clavain, Laura
Erdemir, Aysegul
Lewis, Caroline A.
Date Issued
May 2018
Journal
Cell Stem Cell
Publisher
Elsevier BV
Citation
Mihaylova, Maria M. et al. "Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging." Cell Stem Cell 22 (2018): 769-778 © 2018 The Author(s)
Version
Author's final manuscript
Abstract
Diet has a profound effect on tissue regeneration in diverse organisms, and low caloric states such as intermittent fasting have beneficial effects on organismal health and age-associated loss of tissue function. The role of adult stem and progenitor cells in responding to short-term fasting and whether such responses improve regeneration are not well studied. Here we show that a 24 hr fast augments intestinal stem cell (ISC) function in young and aged mice by inducing a fatty acid oxidation (FAO) program and that pharmacological activation of this program mimics many effects of fasting. Acute genetic disruption of Cpt1a, the rate-limiting enzyme in FAO, abrogates ISC-enhancing effects of fasting, but long-term Cpt1a deletion decreases ISC numbers and function, implicating a role for FAO in ISC maintenance. These findings highlight a role for FAO in mediating pro-regenerative effects of fasting in intestinal biology, and they may represent a viable strategy for enhancing intestinal regeneration. Mihaylova et al. show that short-term fasting promotes intestinal stem and progenitor cell function in young and aged mice by inducing a robust fatty acid oxidation (FAO) program. PPARδ agonists emulate these effects, showing that fatty acid metabolism has positive effects on young and old ISCs.
Subjects
Molecular Medicine
Genetics
Cell Biology
MIT Department
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.stem.2018.04.001
