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