bims-exemet 2021-05-16 papers

Med Sci Sports Exerc. 2021 Apr 01. 53(4): 882

DOI: https://doi.org/10.1249/01.mss.0000735220.08496.9d

J Biomed Sci. 2021 May 13. 28(1): 37

Genome wide association study of response to interval and continuous exercise training: the Predict-HIIT study.

BACKGROUND: Low cardiorespiratory fitness (V̇O2peak) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O2peak, there is considerable inter-individual variability in the V̇O2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O2peak response following exercise training.METHODS: Participant change in objectively measured V̇O2peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated (P < 1 × 10-5) with the magnitude of V̇O2peak response. Findings were tested in an independent validation study (n = 39) and compared to previous research.
RESULTS: No variants at the genome-wide significance level were found after adjusting for key covariates (baseline V̇O2peak, individual study, principal components which were significantly associated with the trait). A Quantile-Quantile plot indicates there was minor inflation in the study. Twelve novel loci showed a trend of association with V̇O2peak response that reached suggestive significance (P < 1 × 10-5). The strongest association was found near the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2) gene (rs6959961, P = 2.61 × 10-7). A PPS created from the 12 lead SNPs was unable to predict V̇O2peak response in a tenfold cross validation, or in an independent (n = 39) validation study (P > 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT (P < 1 × 10-4) and the validation study (P < × 10-6), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent.
CONCLUSIONS: Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O2peak response variance, and whether genomic predictors for V̇O2peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .

Keywords: GWAS; Genetics; Individual variability; Polygenic predictor score; V̇O2peak training response

DOI: https://doi.org/10.1186/s12929-021-00733-7

J Clin Endocrinol Metab. 2021 May 13. pii: dgab333. [Epub ahead of print]

New Horizon: Exercise and a Focus on Tissue-Brain Cross Talk.

Logan K Townsend, Rebecca E K MacPherson, David C Wright.

The worlds' population is aging leading to increased rates of neurodegenerative disorders. Exercise has countless health benefits and has consistently been shown to improve brain health and cognitive function. The purpose of this review is to provide an overview of exercise-induced adaptations in the brain with a focus on crosstalk between peripheral tissues and the brain. We highlight recent studies into exercise-induced circulating factors, or exerkines, including irisin, cathepsin B, GPLD1, ketones, and the mechanisms mediating their effects in the brain.

Keywords: BDNF; BRAIN; EXERCISE; FGF21; GDF15; GPLD1; IRISIN

DOI: https://doi.org/10.1210/clinem/dgab333

Am J Physiol Endocrinol Metab. 2021 May 10.

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.

Kikumi D Ono-Moore, I Mark Olfert, Jennifer M Rutkowsky, Sree V Chintapalli, Brandon J Willis, Michael L Blackburn, D Keith Williams, Juliana O'Reilly, Todd Tolentino, K C Kent Lloyd, Sean H Adams.

Myoglobin (Mb) is a regulator of O2 bioavailability in type I muscle and heart, at least when tissue O2 levels drop. Mb also plays a role in regulating cellular NO pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggests additional roles in muscle intermediary metabolism and fuel selection. To evaluate this hypothesis, we measured energy expenditure (EE), respiratory exchange ratio (RER), body weight gain and adiposity, glucose tolerance and insulin sensitivity in Mb knockout (Mb-/-) and wildtype (WT) mice challenged with a high fat diet (HFD, 45% of calories). In males (n=10/genotype) and females (n=9/genotype) aged 5-6, 11-12, and 17-18 wk, there were no genotype effects on RER, EE, or food intake. RER and EE during cold (10˚C, 72 h), and glucose and insulin tolerance, were not different compared to within-sex WT controls. At ~18 and ~19 wk of age, female Mb-/- adiposity was ~42-48% higher vs. WT females (p=0.1). Transcriptomics analyses (whole gastrocnemius, soleus) revealed few consistent changes, with the notable exception of a 20% drop in soleus transferrin receptor (Tfrc) mRNA. Capillarity indices were significantly increased in Mb-/-, specifically in Mb-rich soleus and deep gastrocnemius. The results indicate that Mb loss does not have a major impact on whole-body glucose homeostasis, EE, RER, or response to a cold challenge in mice. However, the greater adiposity in female Mb-/- mice indicates a sex-specific effect of Mb KO on fat storage and feed efficiency.

Keywords: globin; heme; hypoxia; neovascularization; nitric oxide

DOI: https://doi.org/10.1152/ajpendo.00624.2020

Front Physiol. 2021 ;12 660068

Physical Exercise: A Novel Tool to Protect Mitochondrial Health.

Daniela Sorriento, Eugenio Di Vaia, Guido Iaccarino.

Mitochondrial dysfunction is a crucial contributor to heart diseases. Alterations in energetic metabolism affect crucial homeostatic processes, such asATP production, the generation of reactive oxygen species, and the release of pro-apoptotic factors, associated with metabolic abnormalities. In response to energetic deficiency, the cardiomyocytes activate the Mitochondrial Quality Control (MQC), a critical process in maintaining mitochondrial health. This process is compromised in cardiovascular diseases depending on the pathology's severity and represents, therefore, a potential therapeutic target. Several potential targeting molecules within this process have been identified in the last years, and therapeutic strategies have been proposed to ameliorate mitochondria monitoring and function. In this context, physical exercise is considered a non-pharmacological strategy to protect mitochondrial health. Physical exercise regulates MQC allowing the repair/elimination of damaged mitochondria and synthesizing new ones, thus recovering the metabolic state. In this review, we will deal with the effect of physical exercise on cardiac mitochondrial function tracing its ability to modulate specific steps in MQC both in physiologic and pathologic conditions.

Keywords: cardiovascular disease; energetic metabolism; heart; mitochondrial dysfunction; physical activity

DOI: https://doi.org/10.3389/fphys.2021.660068

Exerc Immunol Rev. 2021 ;27 125-141

Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach.

Francisco Llavero, Lidia B Alejo, Carmen Fiuza-Luces, Alejandro López Soto, Pedro L Valenzuela, Adrián Castillo-García, Javier S Morales, David Fernández, Itziar Pagola Aldazabal, Manuel Ramírez, Alejandro Santos-Lozano, José L Zugaza, Alejandro Lucia.

BACKGROUND: Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40±6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state.METHODS: Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach.
RESULTS: A significant time effect was found for NK cell cytotoxicity (p<0.001), which was increased ~10-fold at both midand post-intervention versus baseline. No significant intervention effect was found for NK surface receptor expression, except for CXCR3 determined as mean fluorescence intensity (p=0.044, although with no significant differences in post hoc pairwise comparisons). The proteins showing a higher differential expression (Log2 fold-change > 10 and false discovery rate [FDR] q-value < 0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR p<25%) were found: two related to transmembrane transport and cellular composition (downregulated at mid-intervention vs baseline), and two related to oxidation- reduction reactions (regulated at post-intervention versus baseline).
CONCLUSION: A progressive exercise intervention of MICT followed by HIIT induces a remarkable improvement in NK function compared with the untrained state, although at the mechanistic level the pathways involved seem to differ over time during the intervention.

Keywords: NK cell; cytotoxicity; high interval training; immune system

Adv Exp Med Biol. 2021 ;1269 101-105

Effects of Exercise Training on Cardiac and Skeletal Muscle Functions in Patients with Chronic Heart Failure.

Tsubasa Watanabe, Norio Murase, Ryotaro Kime, Yuko Kurosawa, Sayuri Fuse, Takafumi Hamaoka.

The primary symptom in patients with chronic heart failure (CHF) is exercise intolerance. Previous studies have reported that reduced exercise tolerance in CHF can be explained not only by cardiac output (a central factor) but also by reduced skeletal muscle aerobic capacity (a peripheral factor). Although exercise training in CHF improves exercise tolerance, few studies have evaluated the effects of exercise training on each specific central and peripheral factor in CHF. The aim of this study was to investigate the central and peripheral aerobic functions in CHF and the effects of exercise training in CHF on cardiac output and skeletal muscle deoxygenation during exercise. We assessed peak oxygen uptake (VO2) during cardiopulmonary exercise testing, peak cardiac output (CO) using noninvasive hemodynamic monitoring, and muscle oxygen saturation (SmO2) using near-infrared spectroscopy (NIRS). Patients with CHF were trained for 12 weeks and performed ramp cycling exercise until exhaustion before and after the exercise training. Peak VO2, peak CO, and SmO2 changes from rest to peak exercise (ΔSmO2) were significantly lower in CHF than those in healthy subjects. As a result of exercise training, peak oxygen uptake in patients with CHF was improved and positively associated with change in ΔSmO2. In contrast, there was no change in peak cardiac output. The results of this study indicate that both cardiac and skeletal muscle functions in patients with CHF were lower than those in healthy subjects. Further, the results suggest that the improvement of exercise capacity in patients with CHF by exercise training was related to the improved utilization of oxygen (a peripheral factor) in skeletal muscle.

Keywords: Cardiac rehabilitation; Chronic heart failure; Exercise capacity; Near-infrared spectroscopy; Skeletal muscle

DOI: https://doi.org/10.1007/978-3-030-48238-1_16