Current Evidence of the Role of the Myokine Irisin in Cancer.

Cancer is a disease associated with extreme human suffering, a huge economic cost to health systems, and is the second leading cause of death worldwide. Regular physical activity is associated with many health benefits, including reduced cancer risk. In the past two decades, exercising/contracting skeletal muscles have been found to secrete a wide range of biologically active proteins, named myokines. Myokines are delivered, via the circulation, to different cells/tissues, bind to their specific receptors and initiate signaling cascades mediating the health benefits of exercise. The present review summarizes the existing evidence of the role of the myokine irisin in cancer. In vitro studies have shown that the treatment of various cancer cells with irisin resulted in the inhibition of cell proliferation, survival, migration/ invasion and induced apoptosis by affecting key proliferative and antiapoptotic signaling pathways. However, the effects of irisin in humans remains unclear. Although the majority of the existing studies have found reduced serum irisin levels in cancer patients, a few studies have shown the opposite. Similarly, the majority of studies have found increased levels of irisin in cancer tissues, with a few studies showing the opposite trend. Clearly, further investigations are required to determine the exact role of irisin in cancer.

Changes in Inflammatory Cytokines and Irisin in Response to High Intensity Swimming in Adolescent versus Adult Male Swimmers.

Swimming is a popular youth sport that is considered beneficial for cardiovascular fitness. However, the potential inflammatory outcomes of high intensity swimming in younger swimmers are unclear, as is the response of irisin, a myokine released during exercise with anti-inflammatory properties. This study compared the plasma concentrations of interleukins 1-beta (IL-1ß), 6 (IL-6), 10 (IL-10), tumor necrosis factor alpha (TNF-α) and irisin in response to intense swimming between adolescent and adult male swimmers. Thirty-two swimmers (16 adolescents, 14 ± 1 years; 16 adults, 21.5 ± 3.1 years) completed a high intensity interval swimming trial. At rest, only TNF-α was higher (33%, p < 0.05) in adolescents compared with adults. There was an overall significant increase in IL-1ß from pre- to post-swimming (3% in adolescents, 24% in adults), but no significant interaction. IL-10 significantly increased in both groups (+34% in adolescents, +56% in adults). IL-6 and TNF-α increased significantly (+32% and +26%, respectively) in adults, but not in adolescents (+2% and -9%, respectively). Adults showed a small, but significant decrease in irisin (-5%), with no change in adolescents. The lack of an IL-6, TNF-α and irisin response to intense swimming in adolescent swimmers may suggest a blunted inflammatory and myokine response following high intensity exercise in trained youth.

Osteokines and Bone Markers at Rest and following Plyometric Exercise in Pre- and Postmenopausal Women.

The effect of plyometric exercise on bone biomarkers has been studied in pediatric and young adult populations in order to better understand how exercise influences bone homeostasis. However, there are no such data in postmenopausal women, a group characterized by an uncoupling of the bone resorption-formation cycle. This study examined the serum concentrations of sclerostin, dickkopf-1 (DKK1), c-terminal crosslinking telopeptides of type I collagen (CTXI), and procollagen type I amino-terminal propeptide (PINP) at rest and following a single bout of plyometric exercise in 20 premenopausal (23.1 ± 2.3 years) and 20 postmenopausal women (57.9 ± 4.3 years). The exercise consisted of 128 jumps, organized into 5 circuit stations. Blood samples were obtained prior to and 5 min, 1 h, and 24 h postexercise. At rest, postmenopausal women had significantly higher sclerostin and CTXI, but lower DKK1 than premenopausal women. Sclerostin increased 5 min postexercise only in the premenopausal group. DKK1 decreased 24 h postexercise in the premenopausal women while it decreased 1 h postexercise in the postmenopausal women. In both groups, CTXI did not change across time and PINP decreased 5 min and 1 h postexercise (p < 0.05). The PINP/CTXI ratio decreased 5 min and 1 h postexercise then significantly increased 24 h postexercise only in premenopausal women. These results indicate that although plyometric exercise is effective in eliciting osteoanabolic effects in younger women; such an effect is not evident in postmenopausal women.

Dairy product intake decreases bone resorption following a 12-week diet and exercise intervention in overweight and obese adolescent girls.

BACKGROUND: We examined whether increased dairy intake was associated with changes in the levels of bone-related biochemical markers in overweight/obese adolescent girls undergoing a 12-week diet and exercise intervention. METHODS: Thirty-five girls were assigned to a low dairy group (LDa; 0-2 servings/day; n = 16) or a higher dairy group (RDa; 4 servings/day; n = 19). Morning, fasted/resting blood samples were collected before and after the intervention and serum concentrations of procollagen-type-1-N-terminal-propeptide (P1NP), ß-isomerized-C-terminal-cross-linking-telopeptides (ß-CTX), osteocalcin (OC), 25-hydroxyvitamin-D, sclerostin and parathyroid hormone were measured. RESULTS: At baseline, there were no significant differences between groups in any bone variable. Changes (∆) over time in ß-CTΧ (p = 0.035; interaction) and OC (p = 0.015; interaction) were significantly different between groups characterized by decreases in RDa and increases in LDa. P1NP and P1NP:ß-CTX ratio decreased in both groups (main time effects: p = 0.003, p = 0.041, respectively). ∆ß-CTX (r = -0.37; p = 0.028) and ∆OC (r = -0.39; p = 0.021) were correlated with average number of dairy servings consumed during the study and with each other (r = 0.45; p = 0.006). ∆OC was not correlated with ∆P1NP (r = 0.19; p = 0.27). CONCLUSIONS: Our results suggest that the osteogenic response to a diet and exercise program in this population can be improved with increased dairy intake via a decrease in bone resorption. IMPACT: We demonstrated that bone resorption significantly decreased over the intervention period in the group consuming adequate levels of dairy products compared to the group consuming little to no dairy products. Change in bone resorption was negatively correlated with average number of dairy servings consumed during the study. Our results suggest that the osteogenic response to a diet and exercise program in this population can be improved with increased dairy intake via a decrease in bone resorption. This is the first study to date to assess changes in bone marker status following a lifestyle intervention with exercise and different intakes of dairy products in a sample of OW/OB adolescent girls. We provide evidence that increased dairy product intake is associated with beneficial changes in circulating levels of bone-related biochemical markers in these girls undergoing a 12-week lifestyle (nutrition counseling and exercise training) intervention program. The main impact of our work relates particularly to the recent changes to Canada's food guide. Using the old recommendations, we demonstrated that the inclusion of 3-4 servings of mixed dairy foods per day improved bone health (primarily as a decrease in resorption) in OW/OB adolescent girls and that this level of dairy product intake appears appropriate and should still be encouraged for this age group. We also demonstrated that adolescent girls, a group that usually does not sufficiently consume dairy products, also improved their BMI percentile and nutrient intake with the inclusion of dairy products in their diets.

Cytokine and Sclerostin Response to High-Intensity Interval Running versus Cycling.

PURPOSE: This study examined whether the exercise-induced changes in inflammatory cytokines differ between impact and no-impact high-intensity interval exercise, and whether they are associated with postexercise changes in sclerostin. METHODS: Thirty-eight females (n = 19, 22.6 ± 2.7 yr) and males (n = 19, 22.3 ± 2.4 yr) performed two high-intensity interval exercise trials in random order (crossover design): running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight repetitions of 1 min running or cycling at ≥90% maximal heart rate, separated by 1 min passive recovery intervals. Blood was collected preexercise and 5 min, 1 h, 24 h, and 48 h postexercise, and it was analyzed for serum levels of interleukins (IL-1ß, IL-6, and IL-10), tumor necrosis factor alpha (TNF-α), and sclerostin. RESULTS: Inflammatory cytokines significantly increased over time in both sexes with some differences between trials. Specifically, IL-1ß significantly increased from pre- to 5 min after both trials (23%, P < 0.05), IL-6 increased 1 h after both trials (39%, P < 0.05), IL-10 was elevated 5 min after running (20%, P < 0.05) and 1 h after both running and cycling (41% and 64%, respectively, P < 0.05), and TNF-α increased 5 min after running (10%, P < 0.05). Sclerostin increased 5 min after both trials, with a greater increase in males than that in females (62 vs 32 pg·mL in running, P = 0.018; 63 vs 30 pg·mL in cycling, P = 0.004). In addition, sclerostin was significantly correlated with the corresponding changes in inflammatory cytokines, and 34% of the variance in its postexercise gain score (Δ) was explained by sex and the corresponding gain scores in TNF-α, which was the strongest predictor. CONCLUSION: A single bout of either impact or no-impact high-intensity exercise induces changes in inflammatory cytokines, which are associated with the postexercise increase in sclerostin.

Wnt Signaling-Related Osteokines at Rest and Following Plyometric Exercise in Prepubertal and Early Pubertal Boys and Girls.

PURPOSE: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. METHODS: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-ß ligand (RANKL). RESULTS: Girls had higher resting sclerostin than boys [187.1 (40.1) vs 150.4 (36.4) pg·mL-1, respectively; P = .02]. However, boys had higher DKK-1 [427.7 (142.3) vs 292.8 (48.0) pg·mL-1, respectively; P = .02] and RANKL [3.9 (3.8) vs 1.0 (0.4) pg·mL-1, respectively; P < .01] than girls. In girls, sclerostin significantly decreased 5-minute and 1-hour postexercise (χ2 = 12.7, P = .01), and RANKL significantly decreased 5-minute postexercise (χ2 = 19.1, P < .01) and continued to decrease up to 24-hour postexercise, with large effect sizes. In boys, DKK-1 significantly decreased 1-hour postexercise and remained lower than preexercise 24-hour postexercise (χ2 = 13.0, P = .01). OPG increased in both boys (χ2 = 13.7, P < .01) and girls (χ2 = 11.4, P = .01), with boys having significantly higher OPG at 5-minute and 1-hour postexercise, whereas in girls, this increase was only seen 24-hour postexercise. CONCLUSION: Plyometric exercise induces an overall anabolic osteokine response favoring osteoblastogenesis over osteoclastogenesis in both boys and girls although the timeline and mechanism(s) may be different.

Inhibition of Human Lung Cancer Cell Proliferation and Survival by Post-Exercise Serum Is Associated with the Inhibition of Akt, mTOR, p70 S6K, and Erk1/2.

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and for the most cancer-related deaths. The survival pathway of Akt, its downstream effectors, the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70 S6K), and the Ras-extracellular signal-regulated kinase (Erk1/2) pathways are activated in cancer leading to cell survival and growth. Thus, approaches that inhibit these signaling molecules may prove useful in the fight against lung cancer. Exercise is associated with health benefits and a limited number of studies indicate that serum from physically active individuals inhibit mammary and prostate cancer cell growth. In this study, we examined the effects of post exercise serum on proliferation, survival, and signaling cascades of human NSCLC cells. Blood was collected from male subjects prior to, 5 min, 1 h, and 24 h after a single bout of high intensity interval exercise on a cycle ergometer. Exposure of NSCLC cells to post exercise serum resulted in the inhibition of cell proliferation and survival, as well as significant reduction of phosphorylated/activated Akt, mTOR, p70 S6K, and Erk1/2 levels compared to cells treated with serum taken pre-exercise. Our data suggest that post exercise serum has anti-cancer properties in lung cancer and deserves further systematic investigation in animal models.

Effects of Dairy Consumption on Body Composition and Bone Properties in Youth: A Systematic Review.

Background: According to previous reviews, there is no clear evidence on the effects of dairy consumption on body composition and bone properties in pediatric populations. There is a need for further assessment of existing findings and the methodologic quality of studies before summarizing the evidence. Objective: The aim of the study was to assess the quality, methodologies, and substantive findings of randomized controlled trials (RCTs) that examined the effects of dairy consumption on body size, body composition, and bone properties in children and adolescents. Methods: After searching PubMed and Google Scholar up to December 2016, 15 RCTs were retained and included in this systematic review for further analysis. The quality of the included studies was assessed via the Jadad scale; detailed methodologic and statistical characteristics were evaluated, and the main findings were summarized. Results: The effects of dairy consumption were found to be significant for bone structure and nonsignificant for body size and composition. Eight of the 11 RCTs that assessed bone found significant effects (P < 0.05) for bone mineral content and bone mineral density (BMD), with an average 8% increase in BMD after 16 mo of dairy consumption. Conversely, significant effects (P < 0.05) were found only in 2 of the 14 RCTs that focused on body size (i.e., height and weight) and in only 1 of the 11 RCTs that focused on body composition (i.e., lean mass). Conclusions: The systematic consumption of dairy products may benefit bone structure and development, but it does not appear to affect body composition or body size in children and adolescents. On the basis of the Jadad scale, the methodologic quality of the 15 RCTs was rated as good overall. However, there were methodologic disparities and limitations that may have led to nonsignificant results, particularly for body size and composition. Future RCTs designed to address these limitations are warranted.

Methodological and Statistical Quality in Research Evaluating Nutritional Attitudes in Sports.

The assessment of dietary attitudes and behaviors provides information of interest to sports nutritionists. Although there has been little analysis of the quality of research undertaken in this field, there is evidence of a number of flaws and methodological concerns in some of the studies in the available literature. This review undertook a systematic assessment of the attributes of research assessing the nutritional knowledge and attitudes of athletes and coaches. Sixty questionnaire-based studies were identified by a search of official databases using specific key terms with subsequent analysis by certain inclusion-exclusion criteria. These studies were then analyzed using 33 research quality criteria related to the methods, questionnaires, and statistics used. We found that many studies did not provide information on critical issues such as research hypotheses (92%), the gaining of ethics approval (50%) or informed consent (35%), or acknowledgment of limitations in the implementation of studies or interpretation of data (72%). Many of the samples were nonprobabilistic (85%) and rather small (42%). Many questionnaires were of unknown origin (30%), validity (72%), and reliability (70%) and resulted in low (≤ 60%) response rates (38%). Pilot testing was not undertaken in 67% of the studies. Few studies dealt with sample size (2%), power (3%), assumptions (7%), confidence intervals (3%), or effect sizes (3%). Improving some of these problems and deficits may enhance future research in this field.