Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling
| Autor: | Daniel I. Benjamin, Pieter Both, Joel S. Benjamin, Christopher W. Nutter, Jenna H. Tan, Jengmin Kang, Leo A. Machado, Julian D. D. Klein, Antoine de Morree, Soochi Kim, Ling Liu, Hunter Dulay, Ludovica Feraboli, Sharon M Louie, Daniel K Nomura, Thomas A. Rando |
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| Rok vydání: | 2022 |
| Předmět: |
Blood Glucose
p53 ketosis fasting Physiology muscle Endocrinology Diabetes and Metabolism Medical Biochemistry and Metabolomics Regenerative Medicine Article Myoblasts Endocrinology & Metabolism Endocrinology HDAC stem cells MuSC Humans quiescence Molecular Biology 3-Hydroxybutyric Acid Stem Cells Muscles Cell Biology Fasting Ketosis Stem Cell Research BHB Stem Cell Research - Nonembryonic - Non-Human Biochemistry and Cell Biology Tumor Suppressor Protein p53 diet |
| Zdroj: | Cell metabolism, vol 34, iss 6 Cell Metab |
| Popis: | SummaryShort-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting. |
| Databáze: | OpenAIRE |
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