Heterogeneity of muscle activity during sedentary behavior

Replacing sitting by standing has been hypothesized to reduce the health risks of sitting, based on the assumption that muscles are passive during sitting and active during standing. Interventions have been more effective in overweight (OW) than in normal weight (NW) individuals, but subjects’ muscle activities have not been quantified. This study compared quadriceps and hamstring muscle electromyographic (EMG) activity between 57 NW (body mass index (BMI) 22.5 ± 1.5 kg/m2, female n = 36) and 27 OW (BMI 28.4 ± 2.9 kg/m2, female n = 8) subjects during non-fatiguing standing (15 s, EMGstanding) and sitting (30 min). EMG amplitude was normalized to EMG measured during maximal isometric knee extension and flexion (% EMGMVC), and sitting muscle inactivity and bursts were determined using 4 thresholds (60% or 90% EMGstanding and 1% or 2% EMGMVC). Comparisons were adjusted for sex, age, knee extension strength, and the individual threshold. Standing EMG amplitude was 36% higher in OW (1.9% ± 1.5% EMGMVC) than in NW (1.4% ± 1.4% EMGMVC, P < 0.05) subjects. During sitting, muscles were inactive 89.8% ± 12.7% of the measurement time with 12.7 ± 14.2 bursts/min across all thresholds. On average, 6% more activity was recorded in NW than in OW individuals for 3 of the 4 thresholds (P < 0.05 for 60% or 90% EMGstanding and 1% EMGMVC). In conclusion, the OW group had higher muscle activity amplitude during standing but more muscle inactivity during sitting for 3/4 of the thresholds tested. Interventions should test whether the observed heterogeneity in muscle activity affects the potential to gain cardiometabolic benefits from replacing sitting with standing.

Sp3 Proteins Negatively Regulate β Myosin Heavy Chain Gene Expression during Skeletal Muscle Inactivity

ABSTRACT In adult skeletal muscle, β myosin heavy chain (βMyHC) gene expression is primarily restricted to slow type I fibers; however, its expression is down-regulated in response to muscle inactivity. Little is known about the signaling pathways and transcription factors that mediate this important functional response. This study demonstrates that increased binding of Sp3 to GC-rich elements in theβ MyHC promoter is a critical event in down-regulation ofβ MyHC gene expression under non-weight-bearing conditions. Conversely, binding of Sp3 to these elements decreased while Sp1 binding increased with nuclear extracts from plantaris muscle exposed to mechanical overload, a stimulus that increases βMyHC gene expression. In addition, these experiments revealed the existence of an Sp4-DNA binding complex when using adult skeletal muscle nuclear extract was used but not when nuclear extracts from cultured myotubes were used. Sp3 proteins are competitive inhibitors of Sp1-mediatedβ MyHC reporter gene transactivation in both Drosophila SL-2 and mouse C2C12 myotubes. Sp4 is a weak activator of βMyHC gene expression in SL-2 cells, which lack endogenous Sp1 activity, but does not activate βMyHC gene expression in C2C12 myotubes, which have high levels of Sp1. These results suggest that competitive binding of Sp family proteins regulate βMyHC gene transcription in response to altered neuromuscular activity.

Atrophy responses to muscle inactivity. II. Molecular markers of protein deficits

We examined the expression of several molecular markers of protein balance in response to skeletal muscle atrophy induced by spinal cord isolation (SI; i.e., a complete transection of the spinal cord at both a midthoracic and a high sacral level plus complete deafferentation between the two transection sites). This treatment nearly eliminates neuromuscular activity (activation and loading) of the hindlimb muscles while maintaining neuromuscular connectivity. SI was associated with a reduced transcriptional activity (via pre-mRNA analyses) of myosin heavy chain (MHC) and actin. In addition, there was an increased gene expression of enzyme systems impacting protein degradation (calpain-1; plus enzymes associated with polyubquitination processes) that could further contribute to the protein deficits in the SI muscles via degradative pathways. IGF-I receptor and binding protein-5 mRNA expression was induced throughout the 15-day period of SI, whereas IGF-I mRNA was induced at 8 and 15 days. These responses occurred in the absence of an upregulation of translational regulatory proteins (p70 S6 kinase; eukaryotic 4E binding protein 1) to compensate for the decreased protein translational capacity. These data collectively demonstrate that 1) the molecular changes accompanying SI-induced muscle atrophy are not necessarily the reverse of those occurring during muscle hypertrophy, and 2) the rapid and marked atrophy that defines this model of muscle inactivity is likely the result of multifactorial processes affecting transcription, translation, and protein degradation.