Antioxidant activity of β-lactoglobulin and its modified derivatives

Both native ss-lactoglobulin and its modified derivatives (Figure 1) exhibited antioxidant activity when assessed by the FRAP assay (which measures total reducing power of the sample). A positive correlation was observed between antioxidant activity and protein concentration in all samples. Compared to the native protein, the concentration dependence of the antioxidant activity was significantly greater when ss-lactoglobulin was modified with the Maillard reaction (p=0.000) and Enzyme hydrolysis (p=0.022)....<br /

Correction: Farnfield, M.M., et al. Whey Protein Ingestion Activates mTOR-dependent Signalling after Resistance Exercise in Young Men: A Double-Blinded Randomized Controlled Trial. Nutrients 2009, 1, 263-275.

We found an error in our paper recently published in Nutrients [1]

Exercise-induced activation of STAT3 signaling is increased with age

Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is common to many inflammatory cytokines and growth factors, with recent evidence of involvement in skeletal muscle regeneration. The purpose of this study was to determine whether STAT3 signaling activation is regulated differentially, at rest and following intense resistance exercise, in aged human skeletal muscle. Skeletal muscle biopsies were harvested from healthy younger (n = 11, 20.4 &plusmn; 0.8 years) and older men (n = 10, 67.4 &plusmn; 1.3 years) under resting conditions and 2 h after the completion of resistance exercise. No differences were evident at rest, whereas the phosphorylation of STAT3 was significantly increased in old (23-fold) compared to young (5-fold) subjects after exercise. This correlated with significantly higher induction of the STAT3 target genes including; interleukin-6 (IL-6), JUNB, c-MYC, and suppressor of cytokine signaling (SOCS) 3 mRNA in older subjects following exercise. Despite increased SOCS3 mRNA, cellular protein abundance was suppressed. SOCS3 protein is an important negative regulator of STAT3 activation and cytokine signaling. Thus, in aged human muscle, elevated responsiveness of the STAT3 signaling pathway and suppressed SOCS3 protein are evident following resistance exercise. These data suggest that enhanced STAT3 signaling responsiveness to proinflammatory factors may impact on mechanisms of muscle repair and regeneration.<br /

Effect of ageing and exercise training on myokine expression responses to acute exercise

Age-related muscle loss is a major contributor to falls, fraility and mortality. It has been widely suggested that chronic, age-related inflammation contributes to the gradual loss of skeletal muscle mass that occurs with ageing. Indeed, ageing is associated with elevations in a number of circulating inflammatory proteins, many of which have detrimental effects on skeletal muscle growth and protein balance. Exercise training has been shown to reduce chronic inflammation and, therefore, may represent an appropriate means to reduce age-related inflammation and counteract sarcopenia. Yet few studies have evaluated the effect of aging on skeletal muscle expression of inflammatory proteins and the effect of acute and repeated exercise on these factors. The aim of the current study was to determine the effect of 12 weeks of resistance exercise training on the levels of myokines within skeletal muscle, both at rest and following an acute bout of exercise and to examine how these responses may vary in young and older subjects, thus evaluating the potential for exercise to reduce age-related muscle inflammation. Six healthy young (aged 18-25 years) and 8 healthy older men (aged 60-75 years) completed 12 weeks of resistance exercise training. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of the 12 week training period. Muscle tissue was analyzed for the expression of key inflammatory (MCP-1, IL-8, IL-6 and TNF-α) and anti-inflammatory cytokines (IL-10, IL-13 and IL-4) via bead-based multiplex analysis. Acute exercise increased the expression of inflammatory myokines, while anti-inflammatory myokines remained unchanged. In contrast to the hypothesis for this study, neither age nor training had a significant effect on the expression of myokines within skeletal muscle either in the resting state or 2 hours following exercise. However, older individuals displayed an increased inflammatory response to exercise prior to training when compared to younger individuals. Twelve weeks of resistance exercise training appeared to normalize this difference. Given the variability in myokine levels between individuals and the small subject number in the current study, further research is required to confirm this findin

Intramuscular inflammatory and resolving lipid profile responses to an acute bout of resistance exercise in men

Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. Lipid mediators including classical arachidonic acid-derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro-resolving-mediator metabolites of the omega-3 fatty acids play essential roles in initiation, self-limitation, and active resolution of acute inflammatory responses. In this study, we examined the bioactive lipid mediator profile of human skeletal muscle at rest and following acute resistance exercise. Twelve male subjects completed a single bout of maximal isokinetic unilateral knee extension exercise and muscle biopsies were taken from the m.vastus lateralis before and at 2, 4, and 24&nbsp;h of recovery. Muscle tissue lipid mediator profile was analyzed via liquid chromatography&ndash;mass spectrometry (LC-MS)-based targeted lipidomics. At 2&nbsp;h postexercise, there was an increased intramuscular abundance of cyclooxygenase (COX)-derived thromboxanes (TXB2: 3.33 fold) and prostaglandins (PGE2: 2.52 fold and PGF2&alpha;: 1.77 fold). Resistance exercise also transiently increased muscle concentrations of lipoxygenase (LOX) pathway-derived leukotrienes (12-Oxo LTB4: 1.49 fold and 20-COOH LTB4: 2.91 fold), monohydroxy-eicosatetraenoic acids (5-HETE: 2.66 fold, 12-HETE: 2.83 fold, and 15-HETE: 1.69 fold) and monohydroxy-docosahexaenoic acids (4-HDoHE: 1.69 fold, 7-HDoHE: 1.58 fold and 14-HDoHE: 2.35 fold). Furthermore, the abundance of CYP pathway-derived epoxy- and dihydroxy-eicosatrienoic acids was increased in 2&nbsp;h postexercise biopsies (5,6-EpETrE: 2.48 fold, 11,12-DiHETrE: 1.66 fold and 14,15-DiHETrE: 2.23 fold). These data reveal a range of bioactive lipid mediators as present within human skeletal muscle tissue and demonstrate that acute resistance exercise transiently stimulates the local production of both proinflammatory eicosanoids and pathway markers in specialized proresolving mediator biosynthesis circuits

Molecular networks of human muscle adaptation to exercise and age

Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease