Amino acids such as leucine and its metabolite α-ketoisocaproate (KIC), are returning to be the focus of studies, mainly because of their anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. It is clear that these effects may counteract catabolic conditions, as well as enhance skeletal muscle mass and strength in athletes. Moreover, beta-hydroxy-beta-methylbutyrate (HMB) has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. This review aims to describe the general scientific evidence of KIC and HMB supplementation clinical relevance, as well as their effects (e.g., increases in skeletal muscle mass and/or strength), associated with resistance training or other sports. Moreover, the possible mechanisms of cell signaling regulation leading to increases and/or sparing (during catabolic conditions) of skeletal muscle mass are discussed in detail based on the recent literature.

Long-term adaptation to resistance training is probably due to the cumulative molecular effects of each exercise session. Therefore, we studied in female Wistar rats the molecular effects of a chronic resistance training regimen (3 months) leading to skeletal muscle hypertrophy in the plantaris muscle. Our results demonstrated that muscle proteolytic genes MuRF-1 and Atrogin-1 were significantly decreased in the exercised group measured 24 h after the last resistance exercise session (41.64 and 61.19%, respectively; P < 0.05). Nonetheless, when measured at the same time point, 4EBP-1, GSK-3beta and eIF2Bepsilon mRNA levels and Akt, GSK-3beta and p70S6K protein levels (regulators of translation initiation) were not modified. Such data suggests that if gene transcription constitutes a control point in the protein synthesis pathway this regulation probably occurs in early adaptation periods or during extreme situations leading to skeletal muscle remodeling. However, proteolytic gene expression is modified even after a prolonged resistance training regimen leading to moderate skeletal muscle hypertrophy.

Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats.

Glucocorticoid hormones are important regulators of several physiological processes. Despite having been initially named based on their role in glucose metabolism, glucocorticoids are also fundamental in the regulation of developmental, metabolic, and neurobiological processes, as well as several other biological functions. Due to their involvement in a diverse array of biological pathways, its wide spectrum of action, it is predicted that a wide range of genes may have their expression regulated by the activated glucocorticoid receptor (GR). In fact, it has been demonstrated that in addition to the regulation of several effectors genes, the expression of the gene encoding for GR itself is regulated by physiological stimuli and fine-tuning mechanisms. Importantly, such generalized effector responses and fine-tuning responses seem to be largely mediated by mechanisms of gene regulation. Therefore, this review aims to describe the mechanisms of gene regulation by glucocorticoid hormones, which are capable of regulating differential gene transcription, within a physiological context. From this discussion, we hope to shed light on how a single molecule that is capable of exerting such divergent effects is also capable of promoting such distinct responses in different target tissues.

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known "repeated bout effect", which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, "non-damaging" resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several "low-grade" inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such "less demanding" resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-alpha, IL-10, IL-10/TNF-alpha ratio, and HSP70 levels and mRNA expression of SCF(beta-TrCP), IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-alpha, IL-10, and HSP70 protein expression was carried out by western blotting and SCF(beta-TrCP) (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-alpha and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. In conclusion, exercise training induced decreased TNF-alpha and TLR-4 expressions, resulting in a modified IL-10/TNF-alpha ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inflammation.

Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the “diseasome of physical inactivity”. In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called “acute exercise threshold”, the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: “exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences”. Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a “new” therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.

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583 carbohydrate) were isonitrogenous and isocaloric with only the timing of the drinks differing. A 24 hour stay in a metabolic chamber confirmed negative energy balance while 24-hour urine collections determined nitrogen balance. RESULTS:The 3-day mean nitrogen balance was greater in the PRO + CHO trial (0.008 ± 1.655g N) trial than the CHO trial (-0.568 ± 1.361g N). The mean energy balance was (-188 ± 107 kcal) in the PRO+CHO trial and (-192 ± 74 kcal) in the CHO trial. CONCLUSION:Older individuals in negative energy balance maintain a more positive nitrogen balance by consuming protein after aerobic exercise as opposed to earlier in the day. (No relationships reported)Glucorcorticoids (GC) are well known for their therapeutic anti-inflammatory effects when used acutely and in low doses. In contrast, chronic and/or acute high doses of GC promote several side effects, such as skeletal muscle atrophy and insulin resistance. Therefore, non-pharmacological therapies would minimize side effects induced by GC. Resistance exercise (RE) and leucine (LEU) supplementation increase protein synthesis and improve of glucose homeostasis. (No relationships reported)PURPOSE: The aim of this study was to identify obesity-induced alterations in regulatory mechanisms of skeletal muscle mass and how they would be altered with long term (8 weeks) AMPK-agonist treatment. METHODS:Eight week old male, lean (L) wild type [body weight (BW) = 26.9 g] and ob/ob (O) [BW = 46.2 g] mice were fed an AMP kinase (AMPK) activator,