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Background: Evidence-based comprehensive physical activity programs developed for public schools are abundant yet a theoretical framework for implementation of these programs is lacking. Implementation science in public service organizations is an emerging area of research, but has not been widely successful in the area of physical activity implementation in public schools. Methods: Factors influencing the implementation of physical activity programs in public schools have been explored. Results: To assist federal, state, and local policymakers in developing or enforcing existing policy, this paper provides an integrated theoretical framework, which will address the need for implementation of interventions to increase school-based physical activity programs. Conclusion: We propose a sustainable model of implementation for increasing moderate to vigorous physical activity in public schools using Core Implementation Components theory for organizations and policymakers. more...

Introduction The [beta]3-adrenergic receptor ([beta]3-AR) has long been a therapeutic target to combat obesity and metabolic disease. Since the [beta]3-AR is present in adipose tissue, but not in most other [...], BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains [beta]3-adrenergic receptors ([beta]3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the [beta]3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis. METHODS. Before and after [beta]3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle. RESULTS. The clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and [beta] cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in [beta] cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPAR[gamma] coactivator 1 [alpha] (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001). CONCLUSION. Mirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulinresistant humans. Since [beta] cells and skeletal muscle do not express [beta]3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves [beta] cell function. TRIAL REGISTRATION. Clinicaltrials.gov NCT02919176. FUNDING. NIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998. more...

Recent estimates indicate that up to one-third of elderly people suffer from frailty, characterized by a common set of symptoms including loss of muscle strength, increased fatigability, modest levels of [...], A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength (1,2). Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia (3,4). We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis. more...

The skeletal muscle research field generally accepts that nuclei in skeletal muscle fibers (ie, myonuclei) are post-mitotic and unable to proliferate. Because our deuterium oxide (D2script>O) labeling studies showed DNA synthesis in skeletal muscle tissue, we hypothesized that resident myonuclei can replicate in vivo. To test this hypothesis, we used a mouse model that temporally labeled myonuclei with GFP followed by D2O labeling during normal cage activity, functional overload, and with satellite cell ablation. During normal cage activity, we observed deuterium enrichment into myonuclear DNA in 7 out of 7 plantaris (PLA), 6 out of 6 tibialis anterior (TA), 5 out of 7 gastrocnemius (GAST), and 7 out of 7 quadriceps (QUAD). The average fractional synthesis rates (FSR) of DNA in myonuclei were: 0.0202 ± 0.0093 in PLA, 0.0239 ± 0.0040 in TA, 0.0076 ± 0. 0058 in GAST, and 0.0138 ± 0.0039 in QUAD, while there was no replication in myonuclei from EDL. These FSR values were largely reproduced in the overload and satellite cell ablation conditions, although there were higher synthesis rates in the overloaded PLA muscle. We further provided evidence that myonuclear replication is through endoreplication, which results in polyploidy. These novel findings contradict the dogma that skeletal muscle nuclei are post-mitotic and open potential avenues to harness the intrinsic replicative ability of myonuclei for muscle maintenance and growth. Graphical Abstract [ABSTRACT FROM AUTHOR] more...