Transcriptional response of rat skeletal muscle to prolonged fasting

ABSTRACT: Prolonged fasting-induced changes in rat tibialis anterior muscle transcriptome Skeletal muscle is of primary importance for metabolism, thermogenesis and locomotion. However, muscle integrity is inevitably challenged throughout life, and muscle atrophy occurs in various situations, being associated with development of metabolic diseases. There is virtually no fully effective countermeasure today to fight the loss of muscle mass. It is therfore needed to understand in depth how muscle mass is regulated in wasting conditions. The aim of this study was to decipher the transcriptional regulations involved in prolonged fasting-induced muscle wasting during the phase of protein sparing (P2) and the late phase of increased body protein mobilization (P3). The main findings show that gene expression changes reflect well the intense use of lipids as fuels during P2 and increased use of muscle proteins during P3. Changes in muscle transcriptome for downstream signaling of anabolic and catabolic hormones (Smad, NFKB, EiF2alpha-ATF4, autophagy, ubiquitin-proteasome, Foxo, AMPK, PI3K/AKT, and mTOR pathways) and for the response to oxidative stress, transcription and translation processes, and myogenesis are generally consistent with increased muscle protein degradation and repressed synthesis, in a more marked manner during P3 than P2 compared to the fed state. Nevertheless, several changes appeared to be in favour of muscle protein synthesis during fasting, notably at the level of PI3K/AKT and mTOR pathways, transcription and translations processes, and the response to oxidative stress. They could constitute mechanisms that promote protein sparing during P2 and anticipate refeeding during P3 for restoration of the protein compartment. Future studies should examine validity of such targets for improving nitrogen balance during catabolic diseases.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE149829 | GEO | 2020/10/02

REPOSITORIES: GEO