Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities.

Regular physical activity reduces the risk of several site-specific cancers in humans and suppresses tumour growth in animal models. The mechanisms through which exercise reduces tumour growth remain incompletely understood, but an intriguing and accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. This suggests that exercise can impact tumour biology through direct changes in circulating proteins, RNA molecules and metabolites. Here, we provide a comprehensive narrative overview of what is known about the effects of exercise-conditioned sera on in vitro cancer cell behaviour. In doing so, we consider the key limitations of the current body of literature, both from the perspective of exercise physiology and cancer biology, and we discuss the potential in vivo physiological relevance of these findings. We propose key opportunities for future research in an area that has the potential to identify key anti-oncogenic protein targets and optimise physical activity recommendations for cancer prevention, treatment and survivorship.

A comparison of the health benefits of reduced-exertion high-intensity interval training (REHIT) and moderate-intensity walking in type 2 diabetes patients.

Reduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient intervention that can improve aerobic capacity and insulin sensitivity in sedentary individuals. The present study compared the effects of REHIT and moderate-intensity walking on health markers in patients with type 2 diabetes (T2D) in a counter-balanced crossover study. Sixteen men with T2D (mean ± SD age: 55 ± 5 years, body mass index: 30.6 ± 2.8 kg·m-2, maximal aerobic capacity: 27 ± 4 mL·kg-1·min-1) completed 8 weeks of REHIT (three 10-min low-intensity cycling sessions/week with two "all-out" 10-20-s sprints) and 8 weeks of moderate-intensity walking (five 30-min sessions/week at an intensity corresponding to 40%-55% of heart-rate reserve), with a 2-month wash-out period between interventions. Before and after each intervention, participants underwent an incremental fitness test, an oral glucose tolerance test (OGTT), a whole-body dual-energy X-ray absorptiometry scan, and continuous glucose monitoring. REHIT was associated with a significantly larger increase in maximal aerobic capacity compared with walking (7% vs. 1%; time × intervention interaction effect: p < 0.05). Both REHIT and walking decreased resting mean arterial pressure (-4%; main effect of time: p < 0.05) and plasma fructosamine (-5%; main effect of time: p < 0.05). Neither intervention significantly improved OGTT-derived measures of insulin sensitivity, glycaemic control measured using continuous glucose monitors, blood lipid profile, or body composition. We conclude that REHIT is superior to a 5-fold larger volume of moderate-intensity walking in improving aerobic fitness, but similar to walking REHIT is not an effective intervention for improving insulin sensitivity or glycaemic control in T2D patients in the short term.

No effect of acute and chronic supramaximal exercise on circulating levels of the myokine SPARC.

Myokines may play a role in the health benefits of regular physical activity. Secreted protein acidic rich in cysteine (SPARC) is a pleiotropic myokine that has been shown to be released into the bloodstream by skeletal muscle in response to aerobic exercise. As there is evidence suggesting that SPARC release may be linked to glycogen breakdown and activation of 5' adenosine monophosphate-activated protein kinase, we hypothesised that brief supramaximal exercise may also be associated with increased serum SPARC levels. In the present study, 10 participants (3 women; mean ± SD age: 21 ± 3 y, body mass index (BMI): 22 ± 3 kg m-2, and V˙O2max: 39 ± 6 mL kg-1 min-1) performed an acute bout of supramaximal cycle exercise (20-s Wingate sprint against 7.5% of body mass, with a 1-min warm-up and a 3-min cool-down consisting of unloaded cycling). Serum SPARC levels were determined pre-exercise as well as 0, 15, and 60 min post-exercise and corrected for plasma volume change. To determine whether regular exercise affected the acute SPARC response, participants repeated the acute exercise protocol three times per week for four weeks, and serum SPARC response to supramaximal exercise was reassessed after this period. Acute supramaximal exercise significantly decreased plasma volume (-10%; p < .001), but was not associated with a significant change in serum SPARC levels at either the pre-training or post-training testing sessions. In conclusion, in contrast to aerobic exercise, a single brief supramaximal cycle sprint is not associated with an increase in serum SPARC levels, suggesting that SPARC release is not related to skeletal muscle glycogen breakdown.

M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other monocyte/macrophage subtypes.

BACKGROUND: In obesity, phenotypic switches occur in macrophage populations such that the predominantly M2-polarised anti-inflammatory state seen in lean individuals changes to a predominantly M1-polarised pro-inflammatory state in those who are obese. However, the mechanisms by which these phenotypic shifts occur have not yet been fully elucidated. RESULTS: The effects of oxLDL (1-40 µg/ml; 24 h) on several parameters relevant to the Unfolded Protein Response (UPR)-mediated lipotoxic effects of oxLDL (disruption of ER Ca²âº handling; activation of the UPR transcription factor XBP-1; upregulation of the UPR target genes BiP and CHOP; apoptosis; cell viability) were investigated in human primary monocyte-derived macrophages, and also in monocyte-macrophages derived from the THP-1 monocytic cell line. A consistent pattern was observed: M2-polarised macrophages were more sensitive to the lipotoxic effects of oxLDL than either non-polarised macrophages or non-differentiated monocytic cells. Specifically, M2-polarised macrophages were the only cell type to undergo significantly increased apoptosis (Primary cells: 1.23 ± 0.01 basal; THP-1-derived: 1.97 ± 0.12 basal; P < 0.05 in both cases) and decreased cell viability (Primary cells: 0.79 ± 0.04 basal; THP-1-derived: 0.67 ± 0.02 basal; P < 0.05 in both cases) when exposed to oxLDL levels similar to those seen in overweight individuals (ie. 1 µg/ml). CONCLUSIONS: We propose that the enhanced susceptibility of M2-polarised macrophages to lipotoxicity seen in the present in vitro study could, over time, contribute to the phenotypic shift seen in obese individuals in vivo. This is because a higher degree of oxLDL-induced lipotoxic cell death within M2 macrophages could contribute to a decrease in numbers of M2 cells, and thus a relative increase in proportion of non-M2 cells, within macrophage populations. Given the pro-inflammatory characteristics of a predominantly M1-polarised state, the data presented here may constitute a useful contribution to our understanding of the origin of the pro-inflammatory nature of obesity, and of the pathogenesis of obesity-associated inflammatory disorders such as Type 2 diabetes and atherosclerosis.