PMID- 32825252 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20210413 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 17 DP - 2020 Aug 20 TI - Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats. LID - 10.3390/ijms21175984 [doi] LID - 5984 AB - 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. FAU - Ibrahim, Marianne AU - Ibrahim M AUID- ORCID: 0000-0002-6122-7167 AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Laboratoire de Spectrometrie de Masse Bio-Organique, 25 rue Becquerel, F-67087 Strasbourg, France. FAU - Wasselin, Thierry AU - Wasselin T AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Laboratoire de Spectrometrie de Masse Bio-Organique, 25 rue Becquerel, F-67087 Strasbourg, France. FAU - Challet, Etienne AU - Challet E AUID- ORCID: 0000-0001-9416-9496 AD - Institute of Cellular and Integrative Neurosciences, CNRS, Universite de Strasbourg, F-67000 Strasbourg, France. FAU - Van Dorsselaer, Alain AU - Van Dorsselaer A AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Laboratoire de Spectrometrie de Masse Bio-Organique, 25 rue Becquerel, F-67087 Strasbourg, France. FAU - Le Maho, Yvon AU - Le Maho Y AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Departement Ecologie, Physiologie, Ethologie, 23 rue Becquerel, F-67087 Strasbourg, France. AD - Centre Scientifique de Monaco, 8 quai Antoine 1er, 98000 Monaco, Monaco. FAU - Raclot, Thierry AU - Raclot T AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Departement Ecologie, Physiologie, Ethologie, 23 rue Becquerel, F-67087 Strasbourg, France. FAU - Bertile, Fabrice AU - Bertile F AUID- ORCID: 0000-0001-5510-4868 AD - Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS, Universite de Strasbourg, 67000 Strasbourg, France. AD - Laboratoire de Spectrometrie de Masse Bio-Organique, 25 rue Becquerel, F-67087 Strasbourg, France. LA - eng GR - ANR-05-BLAN-0069/Agence Nationale de la Recherche/ GR - ANR-10-INSB-08-03/Proteomics French Infrastructure (ProFI)/ PT - Journal Article DEP - 20200820 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hormones) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Muscle Proteins) RN - 8W8T17847W (Urea) SB - IM MH - Animals MH - Energy Metabolism/genetics MH - Fasting/*physiology MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Hormones/blood MH - Intercellular Signaling Peptides and Proteins/blood MH - Male MH - Muscle Proteins/*genetics/metabolism MH - Muscle, Skeletal/metabolism/physiopathology MH - Muscular Atrophy/*genetics/metabolism MH - Oxidative Stress/*genetics/physiology MH - Rats, Sprague-Dawley MH - Urea/blood PMC - PMC7503389 OTO - NOTNLM OT - fasting OT - fuel metabolism OT - muscle OT - oxidative stress OT - protein breakdown OT - protein synthesis OT - rat OT - transcriptomics COIS- The authors declare no conflict of interest. EDAT- 2020/08/23 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/09/01 CRDT- 2020/08/23 06:00 PHST- 2020/07/03 00:00 [received] PHST- 2020/08/18 00:00 [revised] PHST- 2020/08/18 00:00 [accepted] PHST- 2020/08/23 06:00 [entrez] PHST- 2020/08/23 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - ijms21175984 [pii] AID - ijms-21-05984 [pii] AID - 10.3390/ijms21175984 [doi] PST - epublish SO - Int J Mol Sci. 2020 Aug 20;21(17):5984. doi: 10.3390/ijms21175984.