Key points
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Contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis and metabolic health, and the associated ...regulatory role of exercise and PGC‐1α.
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We analysed the effects of different short‐ and long‐term exercise regimens on muscle FNDC5 and PGC‐1α, and serum irisin, and studied the associations of irisin and FNDC5 with health parameters.
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FNDC5 and serum irisin did not change after acute aerobic, long‐term endurance training or endurance training combined with resistance exercise (RE) training, or associate with metabolic disturbances. A single RE bout increased FNDC5 mRNA in young, but not older men (27 vs. 62 years). Changes in PGC‐1α or serum irisin were not consistently accompanied by changes in FNDC5.
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Our data suggest that the effects of exercise on FNDC5 and irisin are not consistent, and that their role in health is questionable. Moreover, the regulatory mechanisms should be studied further.
Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC‐1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC‐1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low‐intensity aerobic exercise (AE) (middle‐aged, n= 17), (2) a heavy‐intensity resistance exercise (RE) bout (young n= 10, older n= 11) (27 vs. 62 years), (3) long‐term 21 weeks endurance exercise (EE) training alone (twice a week, middle‐aged, n= 9), or (4) combined EE and RE training (both twice a week, middle‐aged, n= 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC‐1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC‐1α by 4‐fold in young and by 2‐fold in older men, while FNDC5 mRNA only increased in young men post‐RE, by 1.4‐fold. Changes in PGC‐1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer‐term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC‐1α and transcription may regulate FNDC5 expression.
Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of ...overweight women. Previously sedentary overweight women (
= 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum clinical variables were determined with KONELAB instrument. Soluble Vascular Adhesion Protein 1 (VAP-1) was measured with ELISA and its' enzymatic activity as produced hydrogen peroxide. The exercise intervention was effective, as maximal power and maximum rate of oxygen consumption increased while android fat mass decreased. No changes in diet were observed. Metagenomic analysis revealed taxonomic shifts including an increase in
and a decrease in
. These changes were independent of age, weight, fat % as well as energy and fiber intake. Training slightly increased Jaccard distance of genus level β-diversity. Training did not alter the enriched metagenomic pathways, which, according to Bray Curtis dissimilarity analysis, may have been due to that only half of the subjects' microbiomes responded considerably to exercise. Nevertheless, tranining decreased the abundance of several genes including those related to fructose and amino acid metabolism. These metagenomic changes, however, were not translated into major systemic metabolic changes as only two metabolites, phospholipids and cholesterol in large VLDL particles, decreased after exercise. Training also decreased the amine oxidase activity of pro-inflammatory VAP-1, whereas no changes in CRP were detected. All clinical blood variables were within normal range, yet exercise slightly increased glucose and decreased LDL and HDL. In conclusion, exercise training modified the gut microbiome without greatly affecting systemic metabolites or body composition. Based on our data and existing literature, we propose that especially
and
are exercise-responsive taxa. Our results warrant the need for further studies in larger cohorts to determine whether exercise types other than endurance exercise also modify the gut metagenome.
Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the ...prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.
Key points
Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.
Little is known about the effects of high‐intensity interval training (HIT) or of purely ...anaerobic resistance training on AHN.
Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.
We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.
Our results confirm that sustained aerobic exercise is key in improving AHN.
Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high‐intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low‐response trainer (LRT) and high‐response trainer (HRT) adult male rats to various forms of physical exercise for 6–8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin‐positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non‐significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult‐born hippocampal neurons in adult male Sprague–Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise.
Key points
Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents.
Little is known about the effects of high‐intensity interval training (HIT) or of purely anaerobic resistance training on AHN.
Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats.
We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity.
Our results confirm that sustained aerobic exercise is key in improving AHN.
Physical activity is essential in weight management, improves overall health, and mitigates obesity-related risk markers. Besides inducing changes in systemic metabolism, habitual exercise may ...improve gut's microbial diversity and increase the abundance of beneficial taxa in a correlated fashion. Since there is a lack of integrative omics studies on exercise and overweight populations, we studied the metabolomes and gut microbiota associated with programmed exercise in obese individuals. We measured the serum and fecal metabolites of 17 adult women with overweight during a 6-week endurance exercise program. Further, we integrated the exercise-responsive metabolites with variations in the gut microbiome and cardiorespiratory parameters. We found clear correlation with several serum and fecal metabolites, and metabolic pathways, during the exercise period in comparison to the control period, indicating increased lipid oxidation and oxidative stress. Especially, exercise caused co-occurring increase in levels of serum lyso-phosphatidylcholine moieties and fecal glycerophosphocholine. This signature was associated with several microbial metagenome pathways and the abundance of Akkermansia. The study demonstrates that, in the absence of body composition changes, aerobic exercise can induce metabolic shifts that provide substrates for beneficial gut microbiota in overweight individuals.
Kinematic analysis is often performed with a camera system combined with reflective markers placed over bony landmarks. This method is restrictive (and often expensive), and limits the ability to ...perform analyses outside of the lab. In the present study, we used a markerless deep learning-based method to perform 2D kinematic analysis of deep water running, a task that poses several challenges to image processing methods. A single GoPro camera recorded sagittal plane lower limb motion. A deep neural network was trained using data from 17 individuals, and then used to predict the locations of markers that approximated joint centres. We found that 300–400 labelled images were sufficient to train the network to be able to position joint markers with an accuracy similar to that of a human labeler (mean difference < 3 pixels, around 1 cm). This level of accuracy is sufficient for many 2D applications, such as sports biomechanics, coaching/training, and rehabilitation. The method was sensitive enough to differentiate between closely-spaced running cadences (45–85 strides per minute in increments of 5). We also found high test–retest reliability of mean stride data, with between-session correlation coefficients of 0.90–0.97. Our approach represents a low-cost, adaptable solution for kinematic analysis, and could easily be modified for use in other movements and settings. Using additional cameras, this approach could also be used to perform 3D analyses. The method presented here may have broad applications in different fields, for example by enabling markerless motion analysis to be performed during rehabilitation, training or even competition environments.
Different stance widths are commonly utilized when completing the barbell back squat during athletic general preparedness training. Width manipulation is thought to influence sagittal plane stimuli ...to the hip and knee extensors, the primary extensor musculature in the squat. However, how width manipulation affects frontal plane stimuli is less understood. Knowledge of hip and knee net joint moments (NJM) could improve exercise selection when aiming to improve sport‐specific performance and prevent injuries. Fourteen adult amateur rugby athletes were recruited for this study. After a familiarization period, participants performed wide‐ (WIDE, 1.5× greater trochanter width) and narrow‐stance (NARROW, 1× greater trochanter width) barbell back squats to femur parallel depth, using relative loads of 70% and 85% of one‐repetition maximum. Sagittal and frontal plane hip and knee kinetics and kinematics were compared between widths. A Bonferroni‐corrected alpha of 0.01 was employed as the threshold for statistical significance. Knee flexion angle was statistically greater in NARROW than WIDE (P < 0.0001, d = 2.56‐2.86); no statistical differences were observed for hip flexion angle between conditions (P = 0.049‐0.109, d = 0.33‐0.38). Hip‐to‐knee extension NJM ratios and knee adduction NJMs were statistically greater in WIDE than NARROW (P < 0.007, d = 0.51‐1.41). At femur parallel, stance width manipulation in the barbell back squat may provide substantial differences in biomechanical stimulus in both the sagittal plane and the frontal plane. In certain contexts, these differences may have clinically relevant longitudinal implications, from both a performance and a injury prevention standpoint, which are discussed.
Physical activity recommendations for public health include typically muscle-strengthening activities for a minimum of 2 days a week. The range of inter-individual variation in responses to ...resistance training (RT) aiming to improve health and well-being requires to be investigated. The purpose of this study was to quantify high and low responders for RT-induced changes in muscle size and strength and to examine possible effects of age and sex on these responses. Previously collected data of untrained healthy men and women (age 19 to 78 years,
n
= 287 with 72 controls) were pooled for the present study. Muscle size and strength changed during RT are 4.8 ± 6.1 % (range from −11 to 30 %) and 21.1 ± 11.5 % (range from −8 to 60 %) compared to pre-RT, respectively. Age and sex did not affect to the RT responses. Fourteen percent and 12 % of the subjects were defined as high responders (>1 standard deviation (SD) from the group mean) for the RT-induced changes in muscle size and strength, respectively. When taking into account the results of non-training controls (upper 95 % CI), 29 and 7 % of the subjects were defined as low responders for the RT-induced changes in muscle size and strength, respectively. The muscle size and strength responses varied extensively between the subjects regardless of subject’s age and sex. Whether these changes are associated with, e.g., functional capacity and metabolic health improvements due to RT requires further studies.
Resistance training (RT) may improve metabolic health; however, the extent of its effectiveness is constantly evaluated to assess improvements in the group means, thus obscuring the heterogeneous ...individual effects. This study investigated inter‐individual variation in response to RT as reflected in metabolic health indicators and how age, sex, nutrition, and pre‐training phenotypes are associated with such variabilities.
Methods
Previously collected data of men and women (39‐73 years, 135 trained, 73 non‐trained controls) were pooled for analysis. Measurements were taken twice before training to estimate individual day‐to‐day variations and measurement errors (n = 208). The individual responsiveness to the 21‐week RT in cardiometabolic health indicators (ie, systolic blood pressure, high‐density lipoprotein cholesterol (HDL‐C), cholesterol and triglycerides) was determined. Body composition was estimated by bioimpedance and dietary intake according to 4‐day food diaries.
Results
Metabolic responses to RT seemed to be highly individual, and both beneficial and unfavorable changes were observed. Large inter‐individual variations in training response were not explained by a subject's age, sex, body composition, or nutritional status, with the exception of improvements in HDL‐C, which were associated with simultaneous decreases in body fat in older women. The incidence of metabolic syndrome diminished following RT.
Conclusion
This study showed that RT could improve some specific metabolic health indicators beyond normal day‐to‐day variations, especially in blood lipid profile. Further studies are needed to elucidate genetic and other mechanisms underlining the heterogeneity of RT responses. This knowledge may be useful in providing individually tailored exercise prescriptions as part of personalized preventative health care.
The purpose of this study was to examine the reliability and validity of the “panoramic” brightness mode ultrasonography (US) method to detect training-induced changes in muscle cross-sectional area ...(CSA) by comparison with results obtained using magnetic resonance imaging (MRI). Out of 27 young male volunteers, 20 subjects were assigned to training group and seven to non-training control group. Muscle CSAs of vastus lateralis were analyzed by MRI and US before and after 21 weeks of either heavy resistance training or control period. Measured by both the US and MRI, the resistance training induced significant increases (~13–14%,
P
< 0.001) in muscle CSA, whereas no changes were observed in control group. A high repeatability was found between the two consequent US measurements (intraclass correlation coefficient, ICC of 0.997) with standard error of measurement (SEM) of 0.38 cm
2
and smallest detectable difference of 1.1 cm
2
. Validity of the US method against MRI in assessing CSA of VL produced ICC of 0.905 and SEM of 0.87 cm
2
with high limits of agreement analyzed by Bland and Altman method. However, the MRI produced systematically (10 ± 4%,
P
< 0.01) larger CSA values than the US method. The US showed high agreement against MRI in detecting changes in muscle CSA (ICC of 0.929, SEM of 0.94 cm
2
). The results of this study showed that the panoramic US method provides repeatable measures of a muscle CSA although MRI produced larger absolute CSA values. Moreover, this US method detects training-induced changes in muscle CSA with a comparable degree of precision to MRI.
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