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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mihaylova, MM; Cheng, C-W; Cao, AQ; Tripathi, S; Mana, MD; Bauer-Rowe, KE; Abu-Remaileh, M; Clavain, L; Erdemir, A; Lewis, CA; Freinkman, E; Dickey, AS; La Spada, AR; Huang, Y; Bell, GW; Deshpande, V; Carmeliet, P; Katajisto, P; Sabatini, DM; Yilmaz, ÖH

Published Date

  • May 3, 2018

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 769 - 778.e4

PubMed ID

  • 29727683

Pubmed Central ID

  • 29727683

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2018.04.001

Language

  • eng

Conference Location

  • United States