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•More time spent in accelerometry-measured (i.e., ActiGraph) and self-reported moderate-to-vigorous physical activity was associated with significantly higher skeletal muscle energetics (i.e., ATPmaxand maxOXPHOS).•More time spent in ActiGraph, but not self-reported daily sedentary behavior, was associated with lower skeletal muscle energetics.•Higher activPAL step count, but not time spent in sedentary behavior, was associated with higher ATPmaxand maxOXPHOS.•Older age was associated with lower muscle energetics for men but not women; adjustment for ActiGraph moderate-to-vigorous physical activity attenuated the age association with ATPmaxby 58%, indicating that higher intensity physical activity may offset age-related decline in ATPmax.

Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0–50, higher = greater) and Rating of Perceived Exertion (RPE Fatigability, 6–20, higher = greater) after a slow treadmill walk. Participants from the Study of Muscle, Mobility and Aging (N= 873) were 76.3 ± 5.0 years old, 59.2% women, and 85.3% White. Higher muscle energetics (both in vivo and ex vivo) were associated with lower perceived physical fatigability, all p< 0.03. When stratified by sex, higher ATPmax was associated with lower PFS Physical for men only; higher max OXPHOS and max FAO OXPHOS were associated with lower RPE Fatigability for both sexes. Higher skeletal muscle energetics were associated with 40–55% lower odds of being in the most (PFS ≥ 25, RPE Fatigability ≥ 12) vs least (PFS 0–4, RPE Fatigability 6–7) severe fatigability strata, all p< 0.03. Being a woman was associated with 2–3 times higher odds of being in the most severe fatigability strata when controlling for ATPmax but not the ex vivo measures (p< 0.05). Better mitochondrial energetics were linked to lower fatigability and less severe fatigability in older adults. Findings imply that improving skeletal muscle energetics may mitigate perceived physical fatigability and prolong healthy aging.

Intramyocellular triacylgiycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity., Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, [...]

Muscle-derived stem-cell (MDSC) transplantation presents a promising method for the treatment of muscle injuries. This study investigated the ability of exercise to enhance MDSC transplantation into the injured muscle. Mice were divided into four groups: contusion + phosphate-buffered saline (C + PBS; n= 14 muscles), C + MDSC transplantation (n= 12 muscles), C + PBS + treadmill running (C + PBS + TM; n= 17 muscles), and C + MDSC + TM (n= 13 muscles). One day after injury, the TM groups began running for 1 or 5 weeks. Two days after injury, muscles of C + MDSC and C + MDSC + TM groups were injected with MDSCs. One or 5 weeks later, the number and differentiation of transplanted MDSCs, myofiber regeneration, collagen I formation, and vascularity were assessed histologically. In vitro, MDSCs were subjected to mechanical stimulation, and growth kinetics were quantified. In vitro, mechanical stimulation decreased the MDSC population doubling time (18.6 ± 1.6 h) and cell division time (10.9 ± 0.7 h), compared with the controls (population doubling time: 23.0 ± 3.4 h; cell division time: 13.3 ± 1.1 h) (p= 0.01 and 0.03, respectively). In vivo, 5 weeks of TM increased the myogenic contribution of transplanted MDSCs, compared with the controls (p= 0.02). C + MDSC, C + PBS + TM, and C + MDSC + TM demonstrated decreased fibrosis at 5 weeks, compared with the C + PBS controls (p= 0.00, p= 0.03, and p= 0.02, respectively). Results suggest that the mechanical stimulation favors MDSC proliferation, both in vitroand in vivo, and that exercise enhances MDSC transplantation after injury.