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

Cell Stem Cell. 2018 May 3;22(5):769-778.e4. doi: 10.1016/j.stem.2018.04.001.

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.

Keywords: aging; fasting; fatty acid oxidation; intestinal stem cells; intestine; metabolism; mitochondrial metabolism; stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Cells, Cultured
  • Fasting / metabolism*
  • Fatty Acids / metabolism*
  • Homeostasis*
  • Intestines / cytology*
  • Mice
  • Mice, Inbred Strains
  • Oxidation-Reduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism*

Substances

  • Fatty Acids