Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats

Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fas...

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Main Authors: Marianne Ibrahim, Thierry Wasselin, Etienne Challet, Alain Van Dorsselaer, Yvon Le Maho, Thierry Raclot, Fabrice Bertile
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/17/5984
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author Marianne Ibrahim
Thierry Wasselin
Etienne Challet
Alain Van Dorsselaer
Yvon Le Maho
Thierry Raclot
Fabrice Bertile
author_facet Marianne Ibrahim
Thierry Wasselin
Etienne Challet
Alain Van Dorsselaer
Yvon Le Maho
Thierry Raclot
Fabrice Bertile
author_sort Marianne Ibrahim
collection DOAJ
description Food deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.
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spelling doaj.art-2279eaddf59648ee90fd0ae38a4d65642023-11-20T10:43:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117598410.3390/ijms21175984Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in RatsMarianne Ibrahim0Thierry Wasselin1Etienne Challet2Alain Van Dorsselaer3Yvon Le Maho4Thierry Raclot5Fabrice Bertile6Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceInstitut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceInstitute of Cellular and Integrative Neurosciences, CNRS, Université de Strasbourg, F-67000 Strasbourg, FranceInstitut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceInstitut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceInstitut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceInstitut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Université de Strasbourg, 67000 Strasbourg, FranceFood deprivation resulting in muscle atrophy may be detrimental to health. To better understand how muscle mass is regulated during such a nutritional challenge, the current study deciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, protein mobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and a series of biochemistry measurements. The main findings highlight changes for plasma catabolic and anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidative stress. Changes were generally consistent with the intense use of lipids as fuels during P2. They also reflected increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changes appeared to be in favor of muscle protein synthesis during fasting, notably at the level of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, transcription and translation processes, and the response to oxidative stress. Such mechanisms might promote protein sparing during P2 and prepare the restoration of the protein compartment during P3 in anticipation of food intake for optimizing the effects of an upcoming refeeding, thereby promoting body maintenance and survival. Future studies should examine relevance of such targets for improving nitrogen balance during catabolic diseases.https://www.mdpi.com/1422-0067/21/17/5984fastingtranscriptomicsratmuscleprotein breakdownprotein synthesis
spellingShingle Marianne Ibrahim
Thierry Wasselin
Etienne Challet
Alain Van Dorsselaer
Yvon Le Maho
Thierry Raclot
Fabrice Bertile
Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
International Journal of Molecular Sciences
fasting
transcriptomics
rat
muscle
protein breakdown
protein synthesis
title Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
title_full Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
title_fullStr Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
title_full_unstemmed Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
title_short Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
title_sort transcriptional changes involved in atrophying muscles during prolonged fasting in rats
topic fasting
transcriptomics
rat
muscle
protein breakdown
protein synthesis
url https://www.mdpi.com/1422-0067/21/17/5984
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AT alainvandorsselaer transcriptionalchangesinvolvedinatrophyingmusclesduringprolongedfastinginrats
AT yvonlemaho transcriptionalchangesinvolvedinatrophyingmusclesduringprolongedfastinginrats
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