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. 1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. 2. The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. 3. The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA. 4. The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Faculty of Arts & Sciences, Department of Molecular Biology and Genetics, Yildiz Technical University, 34210 Istanbul, Turkey. 5. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA. 6. Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA. 7. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. 8. Laboratory of Angiogenesis and Neurovascular Link, Department of Oncology, KU Leuven, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, 3000 Leuven, Belgium. 9. Institute of Biotechnology, HiLIFE, University of Helsinki, P.O. Box 56, Helsinki, Finland; Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Stockholm, Sweden. 10. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address: sabatini@wi.mit.edu. 11. The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: ohyilmaz@mit.edu.
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.
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 regenepan class="Species">ration 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.
Authors: Qingling Li; Shuang Deng; Rafael A Ibarra; Vernon E Anderson; Henri Brunengraber; Guo-Fang Zhang Journal: J Biol Chem Date: 2015-02-02 Impact factor: 5.157
Authors: Aravind Subramanian; Pablo Tamayo; Vamsi K Mootha; Sayan Mukherjee; Benjamin L Ebert; Michael A Gillette; Amanda Paulovich; Scott L Pomeroy; Todd R Golub; Eric S Lander; Jill P Mesirov Journal: Proc Natl Acad Sci U S A Date: 2005-09-30 Impact factor: 11.205
Authors: Martin Resnik-Docampo; Christopher L Koehler; Rebecca I Clark; Joseph M Schinaman; Vivien Sauer; Daniel M Wong; Sophia Lewis; Cecilia D'Alterio; David W Walker; D Leanne Jones Journal: Nat Cell Biol Date: 2016-12-19 Impact factor: 28.824
Authors: Massimiliano Cerletti; Young C Jang; Lydia W S Finley; Marcia C Haigis; Amy J Wagers Journal: Cell Stem Cell Date: 2012-05-04 Impact factor: 24.633
Authors: Nick Barker; Johan H van Es; Jeroen Kuipers; Pekka Kujala; Maaike van den Born; Miranda Cozijnsen; Andrea Haegebarth; Jeroen Korving; Harry Begthel; Peter J Peters; Hans Clevers Journal: Nature Date: 2007-10-14 Impact factor: 49.962
Authors: Bo Wang; Xin Rong; Elisa N D Palladino; Jiafang Wang; Alan M Fogelman; Martín G Martín; Waddah A Alrefai; David A Ford; Peter Tontonoz Journal: Cell Stem Cell Date: 2018-02-01 Impact factor: 25.269
Authors: Rachel R Stine; Alexander P Sakers; Tara TeSlaa; Megan Kissig; Zachary E Stine; Chan Wook Kwon; Lan Cheng; Hee-Woong Lim; Klaus H Kaestner; Joshua D Rabinowitz; Patrick Seale Journal: Cell Stem Cell Date: 2019-09-26 Impact factor: 24.633
Authors: Priya Rangan; Inyoung Choi; Min Wei; Gerardo Navarrete; Esra Guen; Sebastian Brandhorst; Nobel Enyati; Gab Pasia; Daral Maesincee; Vanessa Ocon; Maya Abdulridha; Valter D Longo Journal: Cell Rep Date: 2019-03-05 Impact factor: 9.423