Impaired Pulmonary Vascular Adaptation to Exercise in Emphysema without Pulmonary Hypertension – A Proof-of-Concept Study

Background: Chronic obstructive pulmonary disease with emphysema lead to respiratory disability beyond bronchial obstruction. The functional impact of pulmonary vascular lesions in emphysema remains unknown. We investigated pulmonary vascular adaptation to exercise in patients with extended emphysema.Methods: Chest magnetic resonance imaging was used to quantitatively assess right-heart function, pulmonary artery and distal pulmonary blood flow. This was performed at rest and during cycling exercise with a magnetic resonance imaging-compatible cyclo-ergometer. Seven emphysematous patients without pulmonary hypertension were compared to 7 healthy non-smokers matched in gender and age.Results: At rest, cardio-pulmonary hemodynamics and distal pulmonary vascular parameters were similar in both groups. Intrasubject adaptation to exercise in emphysematous patients was characterized by a higher increase in right-ventricular ejection fraction (ΔRVEF +8.1 vs. -2.4 %, P=0.046) though a lower right-cardiac output (4.41 vs. 5.79 L/min, P=0.04) at exercise. Accounting for right-cardiac output variation, the distal pulmonary vascular yield index trended to be decreased in patients (ΔPBF/ΔQf -0.78 vs. +18.83 %, P=0.18).Conclusions: Pulmonary vascular adaptation to exercise is impaired in emphysematous patients without identified pulmonary hypertension.Clinical trial registration NCT 04126616.

Oxidative Stress, Mitochondrial Function and Adaptation to Exercise: New Perspectives in Nutrition

Cells have the ability to adapt to stressful environments as a part of their evolution. Physical exercise induces an increase of a demand for energy that must be met by mitochondria as the main (ATP) provider. However, this process leads to the increase of free radicals and the so-called reactive oxygen species (ROS), which are necessary for the maintenance of cell signaling and homeostasis. In addition, mitochondrial biogenesis is influenced by exercise in continuous crosstalk between the mitochondria and the nuclear genome. Excessive workloads may induce severe mitochondrial stress, resulting in oxidative damage. In this regard, the objective of this work was to provide a general overview of the molecular mechanisms involved in mitochondrial adaptation during exercise and to understand if some nutrients such as antioxidants may be implicated in blunt adaptation and/or an impact on the performance of exercise by different means.

Exercise Training and Circulating Small Extracellular Vesicles: Appraisal of Methodological Approaches and Current Knowledge

In response to acute exercise, an array of metabolites, nucleic acids, and proteins are enriched in circulation. Collectively termed “exercise factors,” these molecules represent a topical area of research given their speculated contribution to both acute exercise metabolism and adaptation to exercise training. In addition to acute changes induced by exercise, the resting profile of circulating exercise factors may be altered by exercise training. Many exercise factors are speculated to be transported in circulation as the cargo of extracellular vesicles (EVs), and in particular, a sub-category termed “small EVs.” This review describes an overview of exercise factors, small EVs and the effects of exercise, but is specifically focused on a critical appraisal of methodological approaches and current knowledge in the context of changes in the resting profile small EVs induced by exercise training, and the potential bioactivities of preparations of these “exercise-trained” small EVs. Research to date can only be considered preliminary, with interpretation of many studies hindered by limited evidence for the rigorous identification of small EVs, and the conflation of acute and chronic responses to exercise due to sample timing in proximity to exercise. Further research that places a greater emphasis on the rigorous identification of small EVs, and interrogation of potential bioactivity is required to establish more detailed descriptions of the response of small EVs to exercise training, and consequent effects on exercise adaptation.

New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy

Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.

Early postnatal overnutrition impairs VO2max gains with moderate exercise and increase post-exercise muscle damage in adult male rats

Exercise counteracts obesity effects, but information on how early-life obesity may affect long-term adaptation to exercise is lacking. This study investigates the impact of early-life postnatal overfeeding (PO) on animals’ adaptation to exercise. Only male Wistar rats were used. On postnatal day (PN) 30, rats from control (NL-9 pups) or PO (SL-3 pups) litters were separated into four groups: NL-sedentary (NL-Se), NL-exercised (NL-Ex), SL-sedentary (SL-Se), and SL-exercised (SL-Ex). Exercised groups performed moderate-intensity exercise, running on a treadmill, from PN30 to PN90. Further experiments were carried out between PN90 and PN92. PO promoted obesity in SL versus NL rats (P < 0.05). Exercise reduced body weight (P < 0.001), body fat (P < 0.01), and improved glucose homeostasis in SL-Ex versus SL-Se. SL-Ex presented lower VO2max (P < 0.01) and higher post-exercise LDH (P < 0.05) compared to NL-Ex rats. Although moderate exercise counteracted obesity in SL rats, early-life overnutrition restricts fitness gains in adulthood, indicating that early obesity may impair animals’ adaptation to exercise.