Transcriptional Changes Involved in Atrophying Muscles during Prolonged Fasting in Rats
Résumé
Abstract: 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 eects 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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