Elevated muscle mass accompanied by transcriptional and nuclear alterations several months following cessation of resistance‐type training in rats

Abstract

Rodent studies investigating long‐term effects following termination of hypertrophy‐inducing loading have predominantly involved exposures such as synergist ablation and weighted wheel running or ladder climbing. This research yielded a spectrum of results regarding the extent of detraining in terms of muscle mass and myonuclei number. The studies were also limited in their lack of sensitive performance measures and indirect relatedness to resistance training. Our research group developed and validated a relevant rat model of resistance‐type training that induces increased muscle mass and performance. The aim of the present study was to determine to what extent these features persist 3 months following the termination of this training. While performance returned to baseline, muscle mass remained elevated by 17% and a shift in distribution to larger muscle fibers persisted. A 16% greater total RNA and heightened mRNA levels of ribosomal protein S6 kinases implicated preserved transcriptional output and ribosomal content. Remodeling of muscle fiber nuclei was consistent with these findings – increased nuclear number and a distribution shift to a more circular nuclear shape. These findings indicate that muscle mass detrains at a slower rate than performance and implicates multiple forms of myonuclear remodeling in muscle memory.

A molecular signature defining exercise adaptation with ageing and in vivo partial reprogramming in skeletal muscle

“…1 D ), including the potent muscle mass‐regulator JunB (Raffaello et al., 2010) and myonuclear anchor Sun1 (Lei et al., 2009). Perhaps alteration to Sun1 could be related to myonuclear shape changes that occur with exercise training in rodents (Battey et al, 2023; Murach et al., 2020; Rader & Baker, 2022). Collectively, our analysis unearthed a canonical skeletal muscle gene expression signature common between OKSM and exercise adaptation.…”

Going nuclear: Molecular adaptations to exercise mediated by myonuclei

“…Recent evidence also suggests that myonuclei are less elongated with different types of exercise training in rodents. 78 , 79 Myonuclear shape change with exercise could be related to their post-training transcriptional status and role as a mechanosensor. 69 Some evidence suggests that PGC-1α expression, which is induced by exercise in muscle, can alter myonuclear shape.…”

“… 84 , 85 , 86 The most abundant myomiR in skeletal muscle, miR-1, is a presumptive negative regulator of muscle mass by inhibiting factors in the IGF-1/PI3k/AKT axis, consequently blunting protein synthesis. 79 , 87 MiR-1 also inhibits the gene target of glucose-6-phosphate dehydrogenase ( G6pdx) , the rate-limiting enzyme in the pentose phosphate pathway, potentially contributing to metabolic reprogramming during muscle loading. 88 , 89 MiR-1 decreases acutely and chronically in response to RE training.…”

The myonuclear domain in adult skeletal muscle fibres: past, present and future

“…These data provide some evidence for a spatial component to myonuclear transcriptional activity. Myonuclei also change shape in response to exercise training in rodents and humans (Murach, Mobley et al., 2020; Rader & Baker, 2022; Battey et al., 2023), which could be linked to myonuclear transcriptional activity and/or movement (Folker et al., 2014; Kirby & Lammerding, 2016; Kirby & Lammerding, 2018). More work is needed on the causes and consequences of changes in myonuclear morphology under different conditions, and the implications for the myonuclear domain.…”