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Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
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International audience. Abstract: Food deprivation resulting in muscle atrophy may be detrimental to health. To betterunderstand how muscle mass is regulated during such a nutritional challenge, the current studydeciphered muscle responses during phase 2 (P2, protein sparing) and phase 3 (P3, proteinmobilization) of prolonged fasting in rats. This was done using transcriptomics analysis and aseries of biochemistry measurements. The main findings highlight changes for plasma catabolicand anabolic stimuli, as well as for muscle transcriptome, energy metabolism, and oxidativestress. 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 markedmanner during P3 than P2 compared to the fed state. Nevertheless, several unexpected changesappeared to be in favor of muscle protein synthesis during fasting, notably at the level of thephosphatidylinositol-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 proteincompartment during P3 in anticipation of food intake for optimizing the eects of an upcomingrefeeding, thereby promoting body maintenance and survival. Future studies should examinerelevance of such targets for improving nitrogen balance during catabolic diseases.
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