Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging.

Cell Stem Cell
Authors
Keywords
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
Journal
Cell Stem Cell
Volume
22
Issue
5
Pages
769-778.e4
Date Published
2018 05 03
ISSN
1875-9777
DOI
10.1016/j.stem.2018.04.001
PubMed ID
29727683
PubMed Central ID
PMC5940005
Links
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