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

Maria M. Mihaylova, Chia Wei Cheng, Amanda Q. Cao, Surya Tripathi, Miyeko D. Mana, Khristian E. Bauer-Rowe, Monther Abu-Remaileh, Laura Clavain, Aysegul Erdemir, Caroline A. Lewis, Elizaveta Freinkman, Audrey S. Dickey, Albert R. La Spada, Yanmei Huang, George W. Bell, Vikram Deshpande, Peter Carmeliet, Pekka Katajisto, David M. Sabatini, Ömer H. Yilmaz

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

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. Mihaylova et al. show that short-term fasting promotes intestinal stem and progenitor cell function in young and aged mice by inducing a robust fatty acid oxidation (FAO) program. PPARδ agonists emulate these effects, showing that fatty acid metabolism has positive effects on young and old ISCs.

Original languageEnglish (US)
Pages (from-to)769-778.e4
JournalCell Stem Cell
Volume22
Issue number5
DOIs
StatePublished - May 3 2018
Externally publishedYes

Keywords

  • aging
  • fasting
  • fatty acid oxidation
  • intestinal stem cells
  • intestine
  • metabolism
  • mitochondrial metabolism
  • stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging'. Together they form a unique fingerprint.

Cite this