Unexpected hypertrophic, phenotypical, and oxidative metabolism transcriptional adaptations in response to resistance training following 10 days of muscle disuse
Authors: Franchi Martino , Sarto Fabio , Sirago Giuseppe , Candia Julian , Hartnell Lisa , Monti Elena , Emiliana Giacomello , Toniolo Luana , De Vito Giuseppe , Ferrucci Luigi , Narici Marco 
Published: May 2023

Introduction: Physical inactivity is a main curse of modern society, characterized by neuromuscular decline with progressive loss of muscle mass, strength, and power and by an increased risk of major chronic diseases. Exercise countermeasures seem to be highly beneficial for contrasting neuromuscular impairments; however, there is a paucity of data regarding recovery programs after muscle disuse. We aimed to study the functional, structural, molecular and transcriptional responses to a 21-day active recovery (AR) program based on resistance training (RT) following 10 days of muscle unloading intervention. Methods: Eleven healthy males (22.1±2.9 y) underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR period, consisting in a RT program for the knee extensors performed at 70% of the 1RM. The data collection was performed at Baseline (BSL), at the end of the ULLS (LS10), and at the end of the exercise recovery period (AR21). Quadriceps femoris (QF) and vastus lateralis (VL) volume and isometric maximum voluntary contraction (MVC) were evaluated. VL muscle architecture and body composition were assessed by ultrasonography and BIA. Histological data (i.e., fibre CSA and type, glycogen content) were evaluated from VL biopsies and transcriptomic profile was investigated by RNA-seq. Results: Following ULLS, QF and VL volume decreased (-3.7% and -3.5%, p<0.05 and p=0.05, respectively) as did MVC (-29.3%, p<0.001) and pennation angle (-3.85%, p<0.05). After the 21-d AR period, MVC and pennation angle were fully restored (+42% and +4.4%, compared to LS10, respectively) whereas QF and VL volume showed a surprising overshoot (+18.6% and +24.2%, p<0.001, compared to LS10, respectively). These changes at whole muscle level were not matched by fiber CSA, as no such changes were observed for both fiber types. However, glycogen staining intensity increased after AR (+14%, p<0.001) as did whole body water content (+3.1%, p<0.05). Transcriptomics analyses showed that the most differentially expressed genes, showing a dampened enrichment after ULLS and a strong re-enrichment following AR, were identified in the hallmarks and pathways related to oxidative phosphorylation, glucose and fatty acid metabolism. These data were accompanied by a reduction of fiber type II distribution at AR21 (-23%, p<0.05) and an increase in fiber type I (+38%, p<0.05). Conclusions: RT successfully recovered functional and structural muscle properties after 10 days of disuse, but in contrast with what usually observed in response to RT, oxidative metabolism and slow fiber type were mostly affected by disuse and recovery, suggesting that muscle could enhance metabolic recovery before hypertrophy per se in response to RT following disuse. Further studies should clarify the responses of such exercise countermeasures after muscle disuse scenarios. The present work was funded by the Italian Space Agency (ASI), MARS-PRE, Project, n. DC-VUM-2017-006. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.