Intermittent fasting:a dietary intervention for prevention of diabetes and cardiovascular disease?

Intermittent fasting, in which individuals fast on consecutive or alternate days, has been reported to facilitate weight loss and improve cardiovascular risk. This review evaluates the various approaches to intermittent fasting and examines the advantages and limitations for use of this approach in the treatment of obesity and type 2 diabetes

From physiology and nutrition to biological sciences, and back again!

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An unexplored role for Peroxiredoxin in exercise-induced redox signalling?

Peroxiredoxin (PRDX) is a ubiquitous oxidoreductase protein with a conserved ionised thiol that permits catalysis of hydrogen peroxide (H2O2) up to a million times faster than any thiol-containing signalling protein. The increased production of H2O2 within active tissues during exercise is thought to oxidise conserved cysteine thiols, which may in turn facilitate a wide variety of physiological adaptations. The precise mechanisms linking H2O2 with the oxidation of signalling thiol proteins (phosphates, kinases and transcription factors) are unclear due to these proteins' low reactivity with H2O2 relative to abundant thiol peroxidases such as PRDX. Recent work has shown that following exposure to H2O2 in vitro, the sulfenic acid of the PRDX cysteine can form mixed disulphides with transcription factors associated with cell survival. This implicates PRDX as an ‘active’ redox relay in transmitting the oxidising equivalent of H2O2 to downstream proteins. Furthermore, under oxidative stress, PRDX can form stable oxidised dimers that can be secreted into the extracellular space, potentially acting as an extracellular ‘stress’ signal. There is extensive literature assessing non-specific markers of oxidative stress in response to exercise, however the PRDX catalytic cycle may offer a more robust approach for measuring changes in redox balance following exercise. This review discusses studies assessing PRDX-mediated cellular signalling and integrates the recent advances in redox biology with investigations that have examined the role of PRDX during exercise in humans and animals. Future studies should explore the role of PRDX as a key regulator of peroxide mediated-signal transduction during exercise in humans

Role of magnetic resonance spectroscopy in cerebral glutathione quantification for youth mental health:A systematic review

AIM: Oxidative stress is strongly implicated in many psychiatric disorders, which has resulted in the development of new interventions to attempt to perturb this pathology. A great deal of attention has been paid to glutathione, which is the brain's dominant antioxidant and plays a fundamental role in removing free radicals and other reactive oxygen species. Measurement of glutathione concentration in the brain in vivo can provide information on redox status and potential for oxidative stress to develop. Glutathione might also represent a marker to assess treatment response. METHODS: This paper systematically reviews studies that assess glutathione concentration (measured using magnetic resonance spectroscopy) in various mental health conditions. RESULTS: There is limited evidence showing altered brain glutathione concentration in mental disorders; the best evidence suggests glutathione is decreased in depression, but is not altered in bipolar disorder. The review then outlines the various methodological options for acquiring glutathione data using spectroscopy. CONCLUSIONS: Analysis of the minimum effect size measurable in existing studies indicates that increased number of participants is required to measure subtle but possibly important differences and move the field forward

Exercise Selectively Mobilises Skin-Homing Effector CD8+ T Cells and Natural Killer Cells into Peripheral Blood.

Introduction: Acute exercise induces a transient mobilisation of lymphocyes into peripheral blood that is largely comprised of CD8+ T cells and natural killer (NK) cells. The magnitude of this response is dependent on the differentiation status of these lymphocyte subsets, thus cells with a capacity to initiate rapid effector function (i.e., cytokine secretion and target killing) exhibit the largest changes in response to exercise. It is hypothesised that the effector cells preferentially mobilised into the bloodstream have high tissue-migrating potential, however, the origin of these cells, and their potential homing destination(s) following exercise has not been established in humans. Accordingly, this study investigated whether CD8+ and NK cell subsets expressing the cutaneous lymphocte antigen (CLA) – a molecule expressed on skin-associated memory lymphocytes (≤ 20% CD8+ T cells and ≤ 50%NK cells) that binds to endothelial cell leukocyte adhesion molecule 1 (ELAM-1) – were selectively mobilised in response to acute exercise. Methods: Ten healthy males (mean ± SD age: 22 ± 3 yrs) completed two different exercise sessions: high-intensity continuous cycling (CC; 85% at HRPeak for 30 mins) and high-intensity interval training (HIIT; 90% of HRpeak 10 x 1 min repetitions with 1 min rest intervals). Blood was taken before, immediately- and 30 min post-exercise for cryo-preservation of peripheral blood mononuclear cells. CD8+ subsets were classified into naive (NA; CD45RA+CCR7+), central memory (CM; CD45RA−CCR7+), effector-memory (EM; CD45RA−CCR7−) and CD45RA- expressing effector-memory cells (EMRA; CD45RA+CCR7−). In parallel, CD56bright ‘regulatory’ and CD56dim ‘cytotoxic’ NK subsets were identified using CD56 and CD16. Lymphocyte subpopulations were examined for CLA expression. Results: The number of CLA+CD8+ cells increased in response to both exercise modes. This observation was driven by a preferential mobilisation of effector-memory CLA+CD8+ T cells, as shown by the percentage change in cell number from baseline to exercise: EMRA (CC 244%, HIIT 86%) \u3e EM (CC 142%, HIIT 75%) \u3e CM (CC 104%, HIIT 51%) \u3e naive (CC 82%, HIIT 34%). Within the NK cell pool, CLA+CD56dim cells (CC 520%, HIIT 326%) were mobilised to a greater extent than CLA+CD56bright cells (CC 180%, HIIT 129%). 30-min post-exercise, there was a reduction in the number of CLA+ cells compared to pre-exercise values. Conclusion: This is the first study to demonstrate a selective mobilisation of skin-homing lymphocytes during exercise, suggesting that exercise redistributes effector cells to peripheral tissue, contributing to immune-surveillance

Low volume–high intensity interval exercise elicits antioxidant and anti-inflammatory effects in humans

The purpose of the present study was to compare acute changes in oxidative stress and inflammation in response to steady state and low volume, high intensity interval exercise (LV-HIIE). Untrained healthy males (n = 10, mean ± s: age 22 ± 3 years; VO2MAX 42.7 ± 5.0 ml · kg−1 · min−1) undertook three exercise bouts: a bout of LV-HIIE (10 × 1 min 90% VO2MAX intervals) and two energy-matched steady-state cycling bouts at a moderate (60% VO2MAX; 27 min, MOD) and high (80% VO2MAX; 20 min, HIGH) intensity on separate days. Markers of oxidative stress, inflammation and physiological stress were assessed before, at the end of exercise and 30 min post-exercise (post+30). At the end of all exercise bouts, significant changes in lipid hydroperoxides (LOOH) and protein carbonyls (PCs) (LOOH (nM): MOD +0.36; HIGH +3.09; LV-HIIE +5.51 and PC (nmol · mg−1 protein): MOD −0.24; HIGH −0.11; LV-HIIE −0.37) were observed. Total antioxidant capacity (TAC) increased post+30, relative to the end of all exercise bouts (TAC (µM): MOD +189; HIGH +135; LV-HIIE +102). Interleukin (IL)-6 and IL-10 increased post+30 in HIGH and LV-HIIE only (P < 0.05). HIGH caused the greatest lymphocytosis, adrenaline and cardiovascular response (P < 0.05). At a reduced energy cost and physiological stress, LV-HIIE elicited similar cytokine and oxidative stress responses to HIGH