The Acute and Chronic Muscle Adaptations Following six weeks of No Load and Traditional High Load Resistance Training

Muscle growth is postulated to occur through mechanisms initiated by local muscle tension. This appears to be true, independent of the external load, provided sufficient tension is achieved. PURPOSE: The purpose of this study was to remove the influence of an external load and compare the acute and chronic muscle adaptations of “No Load” training to traditional High Load training. METHODS: Thirteen participants completed six weeks of thrice weekly unilateral elbow flexion exercise. Using a within subject design, each arm was designated to either the No Load or the High Load (70% one repetition maximum) condition. The No Load condition had the participants repeatedly contract through the full range of motion without the use of body weight or an external load. Muscle size, strength and endurance were measured pre and post training. Acute muscle responses of muscle swelling, fatigue and activation were measured within the training study. RESULTS: Anterior muscle thickness increased pre to post training with no differences between conditions 50% [pre: 2.7 (0.8) vs. post: 2.9 (0.7) cm], 60% [pre: 2.9 (0.7) vs. post: 3.1 (0.7) cm] or 70% [pre: 3.2 (0.7) vs. post: 3.5 (0.7) cm] sites. There was a significant condition x time interaction for one repetition maximum (p=0.017), with High Load (+2.3 kg) increasing more than the No Load condition (+1 kg). For the acute responses, there was a main effect of time for muscle fatigue [pre 40.8 (13.2) vs. post 36 (9.1) Nm p=0.037] and muscle swelling [pre 3.5 (0.6) vs. post 3.8 (0.6) cm, p\u3c0.001]. For the biceps brachii EMG amplitude, the High load condition was greater than the No Load condition for the last three repetitions (p=0.019). Regarding the triceps brachii EMG amplitude, the No Load condition was significantly greater than the High Load condition for the first three and the last three repetitions (p?0.001). Conclusion: Based on these results, muscle growth can occur independent of the external load provided that sufficient local tension is applied to the muscle

The impact of inflammation and acute phase activation in cancer cachexia

The development of cachexia in the setting of cancer or other chronic diseases is a significant detriment for patients. Cachexia is associated with a decreased ability to tolerate therapies, reduction in ambulation, reduced quality of life, and increased mortality. Cachexia appears intricately linked to the activation of the acute phase response and is a drain on metabolic resources. Work has begun to focus on the important inflammatory factors associated with the acute phase response and their role in the immune activation of cachexia. Furthermore, data supporting the liver, lung, skeletal muscle, and tumor as all playing a role in activation of the acute phase are emerging. Although the acute phase is increasingly being recognized as being involved in cachexia, work in understanding underlying mechanisms of cachexia associated with the acute phase response remains an active area of investigation and still lack a holistic understanding and a clear causal link. Studies to date are largely correlative in nature, nonetheless suggesting the possibility for a role for various acute phase reactants. Herein, we examine the current literature regarding the acute phase response proteins, the evidence these proteins play in the promotion and exacerbation of cachexia, and current evidence of a therapeutic potential for patients

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

IL-6 signals through the ubiquitously expressed glycoprotein 130 (gp130) transmembrane protein to activate intracellular signaling that includes signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2). Dynamin-1-like protein (DRP-1) and mitochondrial fission 1 protein (FIS-1) are key proteins in the process of mitochondrial fission and have emerged as IL-6-sensitive targets. The purpose of this study was to examine the regulation of DRP-1 and FIS-1 expression by IL-6 and gp130 signaling in myotubes and skeletal muscle. Fully differentiated C2C12 myotubes were treated with 100 ng of IL-6 for 24 hours in the presence of gp130siRNA, C188-9 (STAT3 inhibitor), or PD98059 (ERK1/2 inhibitor). Male C57BL/6 (B6) and muscle-specific gp130 knockout mice (KO) had IL-6 systemically overexpressed for 2 weeks by transient transfection with 50 ng of an IL-6-expressing or control plasmid in the quadriceps muscles, and the tibialis anterior muscle was analyzed to determine systemic effects of IL-6. IL-6 induced DRP-1 and FIS-1 expression in myotubes 124% and 82% (p=.001) and in skeletal muscle 97% and 187% (p=.001). Myotube gp130 knockdown suppressed the IL-6 induction of DRP-1 68% (p=.002) and FIS-1 65% (p=.001). Muscle KO suppressed the IL-6 induction of DRP-1 220% (p=.001) and FIS-1 121% (p=.001). ERK1/2 inhibition suppressed the IL-6 induction of DRP-1 59% (p=.0003) and FIS-1 102% (p=.0001) in myotubes, while there was no effect of STAT3 inhibition. We report that chronically elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes

Inflammatory signalling regulates eccentric contraction‐induced protein synthesis in cachectic skeletal muscle

Abstract Background Skeletal muscle responds to eccentric contractions (ECC) with an anabolic response that involves the induction of protein synthesis through the mechanistic target of rapamycin complex 1. While we have reported that repeated ECC bouts after cachexia initiation attenuated muscle mass loss and inflammatory signalling, cachectic muscle's capacity to induce protein synthesis in response to ECC has not been determined. Therefore, we examined cachectic muscle's ability to induce mechano‐sensitive pathways and protein synthesis in response to an anabolic stimulus involving ECC and determined the role of muscle signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB) signalling on ECC‐induced anabolic signalling. Methods Mechano‐sensitive pathways and anabolic signalling were examined immediately post or 3 h after a single ECC bout in cachectic male ApcMin/+ mice (n = 17; 16 ± 1% body weight loss). Muscle STAT3/NFκB regulation of basal and ECC‐induced anabolic signalling was also examined in an additional cohort of ApcMin/+ mice (n = 10; 16 ± 1% body weight loss) that received pyrrolidine dithiocarbamate 24 h prior to a single ECC bout. In all experiments, the left tibialis anterior performed ECC while the right tibialis anterior served as intra‐animal control. Data were analysed by Student's t‐test or two‐way repeated measures analysis of variance with Student‐Newman‐Keuls post‐hoc when appropriate. The accepted level of significance was set at P < 0.05 for all analysis. Results ApcMin/+ mice exhibited a cachectic muscle signature demonstrated by perturbed proteostasis (Ribosomal Protein S6 (RPS6), P70S6K, Atrogin‐1, and Muscle RING‐finger protein‐1 (MuRF1)), metabolic (adenosine monophosphate‐activated protein kinase, Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α), and Cytochrome c oxidase subunit IV (COXIV)), and inflammatory (STAT3, NFκB, extracellular signal‐regulated kinases 1 and 2, and P38) signalling pathway regulation. Nonetheless, mechano‐sensitive signalling pathways (P38, extracellular signal‐regulated kinases 1 and 2, and Protein kinase B (AKT)) were activated immediately post‐ECC irrespective of cachexia. While cachexia did not attenuate ECC‐induced P70S6K activation, the protein synthesis induction remained suppressed compared with healthy controls. However, muscle STAT3/NFκB inhibition increased basal and ECC‐induced protein synthesis in cachectic ApcMin/+ mice. Conclusions These studies demonstrate that mechano‐sensitive signalling is maintained in cachectic skeletal muscle, but chronic STAT3/NFκB signalling serves to attenuate basal and ECC‐induced protein synthesis

Let\u27s talk about sex: where are the young females in blood flow restriction research?

Low-load resistance exercise with the blood flow restriction (BFR) has been shown to increase muscle size similar to that of traditional high-load resistance training. Throughout the BFR literature, there is a vast difference between the quantity of young females included in the literature compared to young males, older males and older females. Therefore, the purpose of this minireview is to discuss the underrepresentation of young females in the BFR literature and review the potential physiologic reasons as to why they may have been excluded. In conclusion, the female menstrual cycle, a normal physiological occurrence, is presumably the reason as to why majority of young females are excluded from participation in BFR studies. Instead of excluding females, we recommend that BFR studies should include both sexes and plot the results separately to determine whether a sex difference exists

Recovery from FOLFOX chemotherapy-induced systemic and skeletal muscle metabolic dysfunction in mice

FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy is used to treat colorectal cancer and can acutely induce metabolic dysfunction. However, the lasting effects on systemic and skeletal muscle metabolism after treatment cessation are poorly understood. Therefore, we investigated the acute and lasting effects of FOLFOX chemotherapy on systemic and skeletal muscle metabolism in mice. Direct effects of FOLFOX in cultured myotubes were also investigated. Male C57BL/6J mice completed four cycles (acute) of FOLFOX or PBS. Subsets were allowed to recover for 4 wk or 10 wk. Comprehensive Laboratory Animal Monitoring System (CLAMS) metabolic measurements were performed for 5 days before study endpoint. C2C12 myotubes were treated with FOLFOX for 24 hr. Acute FOLFOX attenuated body mass and body fat accretion independent of food intake or cage activity. Acute FOLFOX decreased blood glucose, oxygen consumption (V̇o2), carbon dioxide production (V̇co2), energy expenditure, and carbohydrate (CHO) oxidation. Deficits in V̇o2 and energy expenditure remained at 10 wk. CHO oxidation remained disrupted at 4 wk but returned to control levels after 10 wk. Acute FOLFOX reduced muscle COXIV enzyme activity, AMPK(T172), ULK1(S555), and LC3BII protein expression. Muscle LC3BII/I ratio was associated with altered CHO oxidation (r = 0.75, P = 0.03). In vitro, FOLFOX suppressed myotube AMPK(T172), ULK1(S555), and autophagy flux. Recovery for 4 wk normalized skeletal muscle AMPK and ULK1 phosphorylation. Our results provide evidence that FOLFOX disrupts systemic metabolism, which is not readily recoverable after treatment cessation. FOLFOX effects on skeletal muscle metabolic signaling did recover. Further investigations are warranted to prevent and treat FOLFOX-induced metabolic toxicities that negatively impact survival and life quality of patients with cancer.NEW & NOTEWORTHY The present study demonstrates that FOLFOX chemotherapy induces long-lasting deficits in systemic metabolism. Interestingly, FOLFOX modestly suppressed skeletal muscle AMPK and autophagy signaling in vivo and in vitro. The FOLFOX-induced suppression of muscle metabolic signaling recovered after treatment cessation, independent of systemic metabolic dysfunction. Future research should investigate if activating AMPK during treatment can prevent long-term toxicities to improve health and quality of life of patients with cancer and survivors