Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging.
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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. |
Year of Publication | 2018
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Journal | Cell Stem Cell
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Volume | 22
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Issue | 5
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Pages | 769-778.e4
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Date Published | 2018 05 03
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ISSN | 1875-9777
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DOI | 10.1016/j.stem.2018.04.001
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PubMed ID | 29727683
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PubMed Central ID | PMC5940005
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Grant list | R01 CA103866 / CA / NCI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 AG033082 / AG / NIA NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
R00 AG054760 / AG / NIA NIH HHS / United States
R00 AG045144 / AG / NIA NIH HHS / United States
U54 CA224068 / CA / NCI NIH HHS / United States
R01 CA034992 / CA / NCI NIH HHS / United States
R01 CA211184 / CA / NCI NIH HHS / United States
K99 AG054760 / AG / NIA NIH HHS / United States
R01 NS065874 / NS / NINDS NIH HHS / United States
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