| Literature DB >> 29727683 |
Maria M Mihaylova1, Chia-Wei Cheng2, Amanda Q Cao1, Surya Tripathi3, Miyeko D Mana2, Khristian E Bauer-Rowe2, Monther Abu-Remaileh1, Laura Clavain1, Aysegul Erdemir4, Caroline A Lewis5, Elizaveta Freinkman5, Audrey S Dickey6, Albert R La Spada6, Yanmei Huang5, George W Bell5, Vikram Deshpande7, Peter Carmeliet8, Pekka Katajisto9, David M Sabatini10, Ömer H Yilmaz11.
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.Entities:
Keywords: aging; fasting; fatty acid oxidation; intestinal stem cells; intestine; metabolism; mitochondrial metabolism; stem cells
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Year: 2018 PMID： 29727683 PMCID： PMC5940005 DOI： 10.1016/j.stem.2018.04.001
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633