Old skeletal muscle exhibits decreased anabolic sensitivity, eventually contributing to muscle wasting. Besides anabolism, also muscle inflammation and catabolism are critical players in regulating the old skeletal muscle’s sensitivity. Omega-3 fatty acids (ω-3) are an interesting candidate to reverse anabolic insensitivity via anabolic actions. Yet, it remains unknown whether ω-3 also attenuates muscle inflammation and catabolism. The present study investigates the effect of ω-3 supplementation on muscle inflammation and metabolism (anabolism/catabolism) upon resistance exercise (RE). Twenty-three older adults (65–84 years; 8♀) were randomized to receive ω-3 (~3 g/d) or corn oil (placebo [PLAC]) and engaged in a 12-week RE program (3×/wk). Before and after intervention, muscle volume, strength, and systemic inflammation were assessed, and muscle biopsies were analyzed for markers of anabolism, catabolism, and inflammation. Isometric knee-extensor strength increased in ω-3 (+12.2%), but not in PLAC (−1.4%; pinteraction = .015), whereas leg press strength improved in both conditions (+27.1%; ptime < .001). RE, but not ω-3, decreased inflammatory (p65NF-κB) and catabolic (FOXO1, LC3b) markers, and improved muscle quality. Yet, muscle volume remained unaffected by RE and ω-3. Accordingly, muscle anabolism (mTORC1) and plasma C-reactive protein remained unchanged by RE and ω-3, whereas serum IL-6 tended to decrease in ω-3 (pinteraction = .07). These results show that, despite no changes in muscle volume, RE-induced gains in isometric strength can be further enhanced by ω-3. However, ω-3 did not improve RE-induced beneficial catabolic or inflammatory adaptations. Irrespective of muscle volume, gains in strength (primary criterion for sarcopenia) might be explained by changes in muscle quality due to muscle inflammatory or catabolic signaling.

A method to immobilize hFMO3 on magnetic nanoparticles has been described and evaluated in terms of enzyme activity, inhibition, pH stability and reusability.

Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

To improve muscle healing upon injury, it is of importance to understand the interplay of key signaling pathways during muscle regeneration. To study this, mice were injected with cardiotoxin (CTX) or PBS in the Tibialis Anterior muscle and were sacrificed 2, 5 and 12 days upon injection. The time points represent different phases of the regeneration process, i.e. destruction, repair and remodeling, respectively. Two days upon CTX-injection, p-mTORC1 signaling and stress markers such as BiP and p-ERK1/2 were upregulated. Phospho-ERK1/2 and p-mTORC1 peaked at d5, while BiP expression decreased towards PBS levels. Phospho-FOXO decreased two and five days following CTX-injection, indicative of an increase in catabolic signaling. Furthermore, CTX-injection induced a shift in the fiber type composition, characterized by an initial loss in type IIa fibers at d2 and at d5. At d5, new type IIb fibers appeared, whereas type IIa fibers were recovered at d12. To conclude, CTX-injection severely affected key modulators of muscle metabolism and histology. These data provide useful information for the development of strategies that aim to improve muscle molecular signaling and thereby recovery.

Exercise training is considered as a potential intervention to counteract muscle degeneration in cancer cachexia. However, evidence to support such intervention is equivocal. Therefore, we investigated the effect of exercise training, i.e. voluntary wheel running, on muscle wasting, functional capacity, fiber type composition and vascularization during experimental cancer cachexia in mice. Balb/c mice were injected with PBS (CON) or C26 colon carcinoma cells to induce cancer cachexia (C26). Mice had free access to a running wheel in their home cage (CONEX and C26EX, n=8-9) or were sedentary (CONS and C26S, n=8-9). Mice were sacrificed 18 days upon tumor cell injection. Immunohistochemical analyes were performed on m. gastrocnemius and quadriceps, and ex vivo contractile properties were assessed in m. soleus and extensor digitorum longus (EDL). Compared with CON, C26 mice exhibited body weight loss (~20%), muscle atrophy (~25%), reduced grip strength (~25%), and lower twitch and tetanic force (~20%) production in EDL but not in m. soleus. Furthermore, muscle of C26 mice were characterizd by a slow-to-fast fiber type shift (type IIx fibers: +57%) and increased capillary density (~30%). In C26 mice, wheel running affect neither body weight loss, nor muscle atrophy or functional capacity, nor inhibited tumor growth. However, wheel running induced a type IIb to type IIa fiber shift in m. quadriceps from both CON and C26, but not in m. gastrocnemius. Wheel running does not exacerbate muscular degeneration in cachexic mice, but, when voluntary, is insufficient to improve the muscle phenotype.

Muscle regeneration is regulated through interaction between muscle and immune cells. Studies showed that treatment with supra-physiological doses of Non-Steroidal Anti-Inflammatory Drug (NSAID) abolished inflammatory signaling and impaired muscle recovery. The present study examines the effects of pharmacologically-relevant NSAID treatment on muscle regeneration. C57BL/6 mice were injected in the tibialis anterior (TA) with either PBS or cardiotoxin (CTX). CTX-injected mice received ibuprofen (CTX-IBU) or were untreated (CTX-PLAC). After 2 days, Il-1β and Il-6 expression was upregulated in the TA of CTX-IBU and CTX-PL vs. PBS. However, Cox-2 expression and macrophage infiltration were higher in CTX-PL vs. PBS, but not in CTX-IBU. At the same time, anabolic markers were higher in CTX-IBU vs. PBS, but not in CTX-PL. Nevertheless, ibuprofen did not affect muscle mass or muscle fiber regeneration. In conclusion, mild ibuprofen doses did not worsen muscle regeneration. There were even signs of a transient improvement in anabolic signaling and attenuation of inflammatory signaling.

Introduction: Since low body weight is an important determinant of success in many sports such as gymnastics, martial arts and figure skating, athletes can benefit from effective weight loss strategies that preserve muscle mass and athletic performance. The present study investigates the effects of increased protein intake and exogenous ketosis on body composition, energy expenditure, exercise capacity, and perceptions of appetite and well-being during a hypocaloric diet in females.Methods: Thirty-two female recreational athletes (age: 22.2 ± .5 years; body weight: 58.3 ± .8 kg; BMI: 20.8 ± .2 kg·m−2) underwent 4 weeks of 30% caloric restriction and were randomized to receive either an increased daily amount of dietary protein (PROT, ∼2.0–2.2 g protein·kg−1·day−1), 3 × 20 g·day−1 of a ketone ester (KE), or an isocaloric placebo (PLA). Body composition was measured by DXA, resting energy expenditure (REE) by indirect calorimetry, exercise capacity during a VO2max test, appetite hormones were measured in serum, and perceptions of general well-being were evaluated via questionnaires.Results: The hypocaloric diet reduced body weight by 3.8 ± .3 kg in PLA, 3.2 ± .3 kg in KE and 2.4 ± .2 kg in PROT (Ptime<.0001). The drop in fat mass was similar between treatments (average: 2.6 ± .1 kg, Ptime<.0001), while muscle mass was only reduced in PLA and KE (average: .8 ± .2 kg, Ptime<.05), and remained preserved in PROT (Pinteraction<.01). REE [adjusted for lean mass] was reduced after caloric restriction in PLA (pre: 32.7 ± .5, post: 28.5 ± .6 kcal·day−1·kg−1) and PROT (pre: 32.9 ± 1.0, post: 28.4 ± 1.0 kcal·day−1·kg−1), but not in KE (pre: 31.8 ± .9, post: 30.4 ± .8 kcal·day−1·kg−1) (Pinteraction<.005). Furthermore, time to exhaustion during the VO2max test decreased in PLA (by 2.5 ± .7%, p < .05) but not in KE and PROT (Pinteraction<.05). Lastly, the perception of overall stress increased in PLA and PROT (p < .05), but not in KE (Pinteraction<.05).Conclusion: Increased protein intake effectively prevented muscle wasting and maintained exercise capacity during a period of caloric restriction in female recreational athletes. Furthermore, exogenous ketosis did not affect body composition, but showed its potential in weight management by preserving a drop in exercise capacity and REE and by improving overall stress parameters during a period of caloric restriction.