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 whe...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/124714 |
| _version_ | 1826198612946714624 |
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| author | Mihaylova, Maria M. Cheng, Chia-Wei Cao, Amanda Q. Tripathi, Surya Mana, Miyeko D. Bauer-Rowe, Khristian E. Abu-Remaileh, Monther Clavain, Laura Erdemir, Aysegul Lewis, Caroline A. Freinkman, Elizaveta Huang, Yanmei Bell, George W. Sabatini, David M. Yilmaz, Ömer H. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research Mihaylova, Maria M. Cheng, Chia-Wei Cao, Amanda Q. Tripathi, Surya Mana, Miyeko D. Bauer-Rowe, Khristian E. Abu-Remaileh, Monther Clavain, Laura Erdemir, Aysegul Lewis, Caroline A. Freinkman, Elizaveta Huang, Yanmei Bell, George W. Sabatini, David M. Yilmaz, Ömer H. |
| author_sort | Mihaylova, Maria M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:07:32Z |
| format | Article |
| id | mit-1721.1/124714 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:07:32Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1247142022-10-01T01:25:24Z Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging Mihaylova, Maria M. Cheng, Chia-Wei Cao, Amanda Q. Tripathi, Surya Mana, Miyeko D. Bauer-Rowe, Khristian E. Abu-Remaileh, Monther Clavain, Laura Erdemir, Aysegul Lewis, Caroline A. Freinkman, Elizaveta Huang, Yanmei Bell, George W. Sabatini, David M. Yilmaz, Ömer H. Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Molecular Medicine Genetics Cell Biology 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. National Institutes of Health (U.S.) (Grant R00 AG045144) National Institutes of Health (U.S.) (Grant R01CA211184) National Institutes of Health (U.S.) (Grant R01CA034992) National Institutes of Health (U.S.) (Grant CA103866) National Institutes of Health (U.S.) (K99 Pathway to Independence award K99AG054760) 2020-04-17T13:27:03Z 2020-04-17T13:27:03Z 2018-05 2020-01-30T14:03:33Z Article http://purl.org/eprint/type/JournalArticle 1934-5909 https://hdl.handle.net/1721.1/124714 Mihaylova, Maria M. et al. "Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging." Cell Stem Cell 22 (2018): 769-778 © 2018 The Author(s) en 10.1016/j.stem.2018.04.001 Cell Stem Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Molecular Medicine Genetics Cell Biology Mihaylova, Maria M. Cheng, Chia-Wei Cao, Amanda Q. Tripathi, Surya Mana, Miyeko D. Bauer-Rowe, Khristian E. Abu-Remaileh, Monther Clavain, Laura Erdemir, Aysegul Lewis, Caroline A. Freinkman, Elizaveta Huang, Yanmei Bell, George W. Sabatini, David M. Yilmaz, Ömer H. Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title | Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title_full | Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title_fullStr | Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title_full_unstemmed | Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title_short | Fasting Activates Fatty Acid Oxidation to Enhance Intestinal Stem Cell Function during Homeostasis and Aging |
| title_sort | fasting activates fatty acid oxidation to enhance intestinal stem cell function during homeostasis and aging |
| topic | Molecular Medicine Genetics Cell Biology |
| url | https://hdl.handle.net/1721.1/124714 |
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