ECSS Paris 2023: OP-PN12
INTRODUCTION: Subcutaneous adipose tissue (SAT) dysfunction is the primary cause of increased ectopic fat deposition (1, 2). Exacerbated production of prooxidant species and capillary rarefaction are considered among the main drivers of adipose tissue dysfunction (3). Conversely, exercise is a well-known regulator of systemic and skeletal redox balance and angiogenesis. Thus, our main aim is to elucidate whether exercise reverses unhealthy adipose tissue expansion. METHODS: Twenty-three sedentary male participants (aged 30-55) were recruited and separated according to their fat percentage (<25%: lean; >25% obese) after DXA scan (HOLOGIC, DiscoveryW[S/N 84165]). The subjects were enrolled in a supervised training on a cycle ergometer (Cyclus II; RBM Electronics, Leipzig, Germany) for 12 weeks. The training consisted of three sessions of 30 min per week at 60% of VO2 peak, then increased to 70% and 80% from baseline at week 4 and 8. Three abdominal SAT biopsies were taken at different time points: 1) baseline 2) post exercise (immediately after the first bout of exercise) and, 3) post-training (after 12-week training). mRNA and protein levels were measured using RT-qPCR and Western Blotting techniques. A mixed-effects analysis was performed, with Tukey's or Sidak's post hoc tests used for multiple comparisons between groups and timepoints respectively. RESULTS: No anthropometric changes were found after 12-week of training, in either the lean or obese groups. Exercise training reduced the mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2; P=0.030), glutathione peroxidase 1 (GPx= P:0.016), catalase (CAT; P= 0.002) and superoxide dismutase 1 (SOD1; P=0.009) in both groups. Vascular endothelial growth factor (VEGF) mRNA levels showed a group effect (P=0.049) with higher levels observed in the lean group compared to the obese group. Meanwhile, NADPH oxidase 2 (NOX2) tended to decrease (P=0.084) after training in both groups. Regarding protein expression, no effect was found in peroxiredoxin 6 (PRDX6), SOD2, SOD3 and CAT protein levels. Increased PRDX1 levels (P=0.025) were found in lean participants compared to obese participants, independently of the timepoint of the study. Higher lipid oxidation was found in the obese group (P=0.011) and was reduced after training (P=0.005). Levels of CD31 remained constant in both groups prior to and following the training period. CONCLUSION: This study demonstrates that three 30-min sessions of low-intensity aerobic exercise per week for twelve weeks are sufficient to promote redox adaptations and reduce lipid peroxidation in obese individuals. However, low-intensity exercise demonstrated no effect on SAT capillarisation. (1) Ioannidou A. Obes Rev. 2022; (2) Luo J. Obesity (Silver Spring). 2025; (3) AlZaim I. Nat Rev Endocrinol. 2023.
Read CV Santiago Ruvira HernandoECSS Paris 2023: OP-PN12
INTRODUCTION: During aging, the heart experiences adverse structural remodelling of the myocardium, which impairs ventricular function and increases the risk of heart failure [1]. Cellular senescence has become increasingly linked to these alterations as senescent cells accumulate with age, displaying permanent cell cycle arrest and dysfunction. In fact, senescent cardiomyocytes and fibroblasts in the myocardium are associated with pathological cardiomyopathies and contractile dysfunction [1]. Senolytics, like Dasatinib and Quercetin (D+Q), are drugs that selectively kill senescent cells and improve myocardial structure and function [1]. Aerobic exercise also has cardioprotective effects and shows promise in reducing cardiac senescence [2]. Therefore, we hypothesized that combining chronic senolytic treatment with aerobic exercise would enact a synergistic reduction of senescence, preserving myocardial structure and function during aging. METHODS: Male and female C57BL/6N mice (12-months-old) were randomly allocated to one of four groups (n=20 per group): naturally aged (VEH), aerobic exercise (2x/week treadmill running; EX), senolytic (D+Q via oral gavage biweekly; SEN) or both combined (exercise and D+Q; SENEX). Interventions lasted 9-months with myocardial structure assessed at the 6- and 9-month timepoints using high frequency ultrasound. A cohort of 4-month-old mice were used as a young control (n=10). Immunofluorescence staining with cardiac troponin T, wheat germ agglutinin, and p16 or p21 was used to measure the area of senescent cardiomyocytes. Senescence was also assessed using western blots for p16 and p21 protein expression from whole heart samples. RESULTS: From 6- to 9-months, the VEH mice displayed a marked decrease in the posterior wall thickness of the left ventricle (LV) (1.41±0.23 to 1.01±0.18 mm) (p<0.05), while the other interventions showed no change. Moreover, cardiomyocytes expressing a senescent marker were smaller in area (345.8±21.7 µm) than those not expressing a senescent marker (367.1±28.3 µm) (p<0.05). VEH hearts had elevated p16 and p21 expression (1.66±1.08 and 1.36±1.16 AU) compared to the YOUNG (0.54±0.29 and 0.20±0.06 AU) (p<0.05), but not any of the interventions. This culminated in a greater LV posterior wall thickening ability in the EX (43.0±6.0 %), SEN (45.5±20.8 %), SENEX (41.0±16.9%), and YOUNG (53.0±28.2 %) compared to the VEH (18.4±10.3 %) (p<0.05). CONCLUSION: Naturally aged mice exhibited elevated senescence as well as LV wall thinning and impaired myocardial function. Moreover, senescent cardiomyocytes had a smaller area, altogether suggesting that senescence drives myocardial atrophy. Importantly, exercise, senolytics, or both combined prevented LV wall thinning and functional declines with a partial removal of senescence, positioning these strategies as promising approaches to mitigate the age-related myocardial remodeling and functional decline. REFERENCES: 1. Luan et al., Cell Death Discov, 2024 2. Werner at al., J Am Coll Cardiol, 2008
Read CV Ryan BevingtonECSS Paris 2023: OP-PN12
INTRODUCTION: Strenuous exercise and high-altitude exposure can disrupt neural activity and impair cognitive functioning. Research suggests that ketone ester (KE) ingestion may counteract cognitive impairments, however, its impact on neural activity during exercise and hypoxia remains unknown. Therefore, we investigated the impact of KE on electroencephalography (EEG) patterns during hypoxia and exercise. METHODS: Twelve healthy males completed three randomized crossover sessions: i) normoxia + placebo (NPL), ii) hypoxia + placebo (HPL), and iii) hypoxia + KE (HKE). Each session included normoxic endurance (ET120’) and high-intensity interval training (HIIT80’), followed by a 16-hour recovery period (including a night), in either normoxia or hypoxia (3,000 m simulated altitude). The next day, participants performed a normoxic 30-min all-out time-trial (TT30’). EEG was recorded in a resting state 2h after the onset of hypoxia, as well as during ET120’, HIIT80’, TT30’, while cerebral tissue oxygenation index (cTOI) was only evaluated at rest. RESULTS: At rest, hypoxia increased alpha and beta power while reducing cTOI (p<0.05 for NPL vs. HPL). KE attenuated the increase in alpha and beta power (alpha: p=0.005, beta: p=0.022, both for HKE vs. HPL), and the drop in cTOI (p=0.019 for HKE vs. HPL). In all conditions, EEG activity rose throughout ET120’ and normalized during a 5-min recovery period (REC), while HIIT80’ elicited a fluctuating neural response that normalized during REC. Independent of the condition, TT30’ increased theta, alpha, and gamma power, which all remained elevated during REC. CONCLUSION: Our data show that KE stabilizes resting-state EEG alterations induced by hypoxia. Moreover, we observed that EEG patterns are distinct for various exercise modalities, showing sustained post-exercise increases in theta, alpha, and gamma power after all-out efforts. These findings suggest that KE can help preserve neural stability under hypoxia and highlight EEG’s potential for monitoring fatigue and tailoring training or recovery strategies.
Read CV Siemon VermeirenECSS Paris 2023: OP-PN12