bims-exemet 2021-07-25 papers

Issue of 2021–07–25
five papers selected by
Javier Botella Ruiz, Victoria University

Physiol Genomics. 2021 Jul 23.

Genetically determined exercise capacity affects systemic glucose response to insulin in rats.

Michael Schwarzer, Annika Molis, Christina Schenkl, Andrea Schrepper, Steven L Britton, Lauren Gerard Koch, Torsten Doenst.

INTRODUCTION: Aerobic exercise capacity is inversely related to morbidity and mortality as well as to insulin resistance. However, exercising in patients has led to conflicting results, presumably because aerobic exercise capacity consists of intrinsic (genetically determined) and extrinsic (environmentally determined) parts. The contribution of both parts to insulin sensitivity is also not clear. We investigated sedentary and exercised (aerobic interval training) high (HCR) and low capacity runners (LCR) differing in their genetically determined aerobic exercise capacity to determine the contribution of both parts to insulin sensitivity.
METHODS AND RESULTS: LCR and HCR differed in their untrained exercise capacity and body weight. Sedentary LCR displayed a diabetic phenotype with higher random glucose, lower glucose infusion rate during hyperinsulinemic euglycemic clamping than HCR. Echocardiography showed equal morphological and functional parameters and no change with exercise. Four weeks of exercise caused significant improvements in aerobic exercise capacity, which was more pronounced in LCR. However, with respect to glucose use, exercise affected HCR only. In these animals, exercise increased 2-deoxyglucose uptake in gastrocnemius (+58.5 %, p= 0.1) and in epididymal fat (+106 %; p<0.05). Citrate synthase activity also increased in these tissues (gastrocnemius 69 % epididymal fat 63 %).
CONCLUSION: In our model of HCR and LCR, genetic predisposition for low exercise capacity is associated with impaired insulin sensitivity and impedes exercise-induced improvements in insulin response. Our results suggest that genetic predisposition for low aerobic exercise capacity impairs insulin response, which may not be overcome by exercise.

Keywords: exercise capacity; exercise training; genetic predisposition; insulin sensitivity

DOI: https://doi.org/10.1152/physiolgenomics.00014.2021

J Biol Chem. 2021 Jul 17. pii: S0021-9258(21)00778-X. [Epub ahead of print] 100976

Increased liver glycogen levels enhance exercise capacity in mice.

Iliana López-Soldado, Joan J Guinovart, Jordi Duran.

Muscle glycogen depletion has been proposed as one of the main causes of fatigue during exercise. However, few studies have addressed the contribution of liver glycogen to exercise performance. Using a low-intensity running protocol, here we analyzed exercise capacity in mice overexpressing protein targeting to glycogen (PTG) specifically in the liver (PTGOE mice), which show a high concentration of glycogen in this organ. PTGOE mice showed improved exercise capacity, as determined by the distance covered and time ran in an extenuating endurance exercise compared to control mice. Moreover, fasting decreased exercise capacity in control mice but not in PTGOE mice. After exercise, liver glycogen stores were totally depleted in control mice, but PTGOE mice maintained significant glycogen levels even in fasting conditions. Additionally, PTGOE mice displayed an increased hepatic energy state after exercise compared to control mice. Exercise caused a reduction in blood glucose concentration in control mice that was less pronounced in PTGOE mice. No changes were found in the levels of blood lactate, plasma free fatty acids, or ß-hydroxybutyrate. Plasma glucagon was elevated after exercise in control mice, but not in PTGOE mice. Exercise-induced changes in skeletal muscle were similar in both genotypes. These results identify hepatic glycogen as a key regulator of endurance capacity in mice, an effect that may be exerted through the maintenance of blood glucose levels.

Keywords: ATP; Exercise; glucose; glycogen; liver metabolism; protein targeting to glycogen (PTG)

DOI: https://doi.org/10.1016/j.jbc.2021.100976

Free Radic Biol Med. 2021 Jul 15. pii: S0891-5849(21)00419-6. [Epub ahead of print]173 1-6

Six weeks of high intensity cycle training reduces H2O2 emission and increases antioxidant protein levels in obese adults with risk factors for type 2 diabetes.

Mathias Flensted-Jensen, Martin Gram, Flemming Dela, Jørn Wulff Helge, Steen Larsen.

Obesity has been associated with increased production of reactive oxygen species (ROS), which may be involved in the development of cardiovascular disease and type 2 diabetes (T2D). Endurance exercise lowers ROS production and increases antioxidant capacity in muscle cells, but it is currently unknown whether high intensity interval training (HIT) elicits the same effects. Twelve sedentary obese subjects at risk of developing T2D took part in a six-week intervention, performing three HIT sessions per week (five 1-min sets of high-intensity cycling (125% of VO2peak), with 90 s recovery in between sets). Muscle biopsies were obtained for assessment of ROS production (H2O2 emission), mitochondrial respiratory capacity, and antioxidant protein levels before and after the intervention. H2O2 emission decreased 60.4% after the intervention (Succinate 3 mmol･l-1), concurrent with a 35.1% increase in protein levels of the antioxidant manganese superoxide dismutase (MnSOD) and a trend towards increased levels of the antioxidant catalase (p = 0.06, 72.9%). These findings were accompanied by a 19% increased mitochondrial respiratory capacity (CI + II), a 6.9% increased VO2peak and a 1.7% lower body fat percentage. These effects were achieved after just 15 min of high-intensity work and 40 min of total time spent per week. Overall, this suggests that a relatively small amount of HIT is sufficient to induce beneficial effects on ROS production and antioxidant status in muscle cells, which may lower oxidative stress and potentially protect against the development of cardiovascular disease.

Keywords: Antioxidants; HIT; Oxidative stress; Skeletal muscle

DOI: https://doi.org/10.1016/j.freeradbiomed.2021.07.020

BMJ Open. 2021 Jul 22. 11(7): e044676

Indicators of response to exercise training: a systematic review and meta-analysis.

Arash Ardavani, Hariz Aziz, Bethan E Phillips, Brett Doleman, Imran Ramzan, Boshra Mozaffar, Philip J Atherton, Iskandar Idris.

BACKGROUND: Means-based analysis of maximal rate of oxygen consumption (VO2max) has traditionally been used as the exercise response indicator to assess the efficacy of endurance (END), high intensity interval (HIIT) and resistance exercise training (RET) for improving cardiorespiratory fitness and whole-body health. However, considerable heterogeneity exists in the interindividual variability response to the same or different training modalities.
OBJECTIVES: We performed a systematic review and meta-analysis to investigate exercise response rates in the context of VO2max: (1) in each training modality (END, HIIT and RET) versus controls, (2) in END versus either HIIT or RET and (3) exercise response rates as measured by VO2max versus other indicators of positive exercise response in each exercise modality.
METHODS: Three databases (EMBASE, MEDLINE, CENTRAL) and additional sources were searched. Both individual response rate and population average data were incorporated through continuous data, respectively. Of 3268 identified manuscripts, a total of 29 studies were suitable for qualitative synthesis and a further 22 for quantitative. Stratification based on intervention duration (less than 12 weeks; more than or equal to 12 weeks) was undertaken.
RESULTS: A total of 62 data points were procured. Both END and HIIT training exhibited differential improvements in VO2max based on intervention duration. VO2max did not adequately differentiate between END and HIIT, irrespective of intervention length. Although none of the other exercise response indicators achieved statistical significance, LT and HRrest demonstrated common trajectories in pooled and separate analyses between modalities. RET data were highly limited. Heterogeneity was ubiquitous across all analyses.
CONCLUSIONS: The potential for LT and HRrest as indicators of exercise response requires further elucidation, in addition to the exploration of interventional and intrinsic sources of heterogeneity.

Keywords: clinical physiology; health policy; sports medicine

DOI: https://doi.org/10.1136/bmjopen-2020-044676

Front Physiol. 2021 ;12 693007

Protein Composition of Circulating Extracellular Vesicles Immediately Changed by Particular Short Time of High-Intensity Interval Training Exercise.

Yoshinao Kobayashi, Akiko Eguchi, Yasuyuki Tamai, Sanae Fukuda, Mina Tempaku, Kiyora Izuoka, Motoh Iwasa, Yoshiyuki Takei, Kenji Togashi.

Introduction/Purpose: High-intensity interval training (HIIT) promotes various biological processes and metabolic effects in multiple organs, but the role of extracellular vesicles (EVs) released from a variety of cells is not fully understood during HIIT exercise (HIIT-Ex). We investigated the changes in circulating number and proteomic profile of EVs to assess the effect of HIIT-Ex.
Methods: Seventeen young men (median age, 20 years) were enrolled in the study. Total duration of the HIIT-Ex was 4 min. Blood samples were collected from before HIIT-Ex (pre-HIIT-Ex), at the immediate conclusion of HIIT-Ex (T0), at 30 min (T30), and at 120 min after HIIT-Ex. The pulse rate and systolic blood pressure were measured. Circulating EVs were characterized, and EV proteins were detected via nano liquid chromatography tandem mass spectrometry.
Results: The pulse rate and systolic blood pressure at T0 to pre-HIIT-Ex were significantly higher. Circulating EV number was significantly altered throughout the HIIT-Ex, and the source of circulating EVs included skeletal muscle, hepatocytes, and adipose tissue. Proteomic analysis identified a total of 558 proteins within isolated circulating EVs from pre-HIIT-Ex, T0, and T30. Twenty proteins in total were significantly changed at pre-HIIT-Ex, T0, and T30 and are involved in a variety of pathways, such as activation of coagulation cascades, cellular oxidant detoxification, and correction of acid-base imbalance. Catalase and peroxiredoxin II were increased at T0.
Conclusion: The circulating EV composition can be immediately changed by particularly a short time of HIIT-Ex, indicating that EVs may intercommunicate across various organs rapidly in response to HIIT-Ex.

Keywords: antioxidant; extracellular vesicle; proteomic analyses; short time of high intensity interval training exercise; skeletal muscle

DOI: https://doi.org/10.3389/fphys.2021.693007