Experimental Physiology最新文献

Altitude training enhances haematological adaptations and endurance at sea level, typically requiring exposure to ∼2500 m altitude for 3-4 weeks. Emerging evidence suggests that low-dose carbon monoxide (CO) inhalation might mimic hypoxia and might be used by elite athletes. In this study, we examine whether periodic low-dose CO exposure can replicate the live-high, train-low model in well-trained individuals, focusing primarily on haematological and performance effects of CO exposure, with haematological markers commonly used to interpret haemoglobin mass changes discussed as exploratory. Eight well-trained individuals (four males and four females) participated in a randomized crossover study. They completed two training blocks of 4 weeks at sea level: one with CO inhalation (INCO) to simulate live-high, train-low and one with ambient air as a control (AIR), separated by a 6 month washout. Haematological variables, in vivo muscle oxidative capacity and performance metrics were assessed before and after each intervention. After INCO, haemoglobin mass (p = 0.018; +53.6 ± 10.8 g. vs. +0.8 ± 11.8 g), red blood cell volume (p = 0.032; +156.6 ± 66.7 mL vs. -65.1 ± 50.7 mL) and blood volume (p = 0.036; +240.4 ± 120.5 mL vs. -208.3 ± 167.5 mL) increased significantly compared with AIR. INCO significantly reduced immature reticulocytes (p = 0.04), but muscle oxidative capacity and performance metrics remained unchanged. These findings suggest that daily low-dose CO exposure at sea level over 4 weeks enhanced haematological adaptations more than standard training but did not affect muscle oxidative capacity or performance.

Ageing negatively affects quality of life and healthspan, and interventions are needed to slow this progressive decline. Previously, we have demonstrated the potential functional benefits of combining a genetically modified probiotic (GMP) targeting the non-canonical arm of the renin-angiotensin system (RAS) with exercise training. Initial RNAseq studies indicated the potential of the interventions to influence circadian physiology. Therefore, the objective of this study was to evaluate the expression of circadian-related genes in the tibialis anterior and soleus muscles in male and female aged rats in response to the administration of the GMP, exercise training and multiple controls. Following 12 weeks of the intervention, circadian-related genes were differentially expressed in male and female aged rats and between tissues, primarily influenced by the exercise intervention, with potential additive effects of the GMP. Several genes were also significantly associated with measures of physical performance. Thus, combining exercise with a RAS-related GMP may have potential functional benefits in late life, potentially related to circadian-related impacts within skeletal muscle.

Exercise training is recommended for individuals with hypertension because it has been shown to lower blood pressure and reverse left ventricular concentric remodelling and mass. However, it is unclear how hypertensive individuals respond in comparison to normotensive individuals and to what extent medical treatment affects the outcome of training. Our aim was to assess the effect of a 6 week high-intensity interval training (HIIT) intervention on cardiac adaptations in subjects with treated or untreated essential hypertension compared with normotensive control subjects. Cardiac function was evaluated by echocardiography in 11 medicated hypertensive men, who adhered to treatment during the intervention but refrained from medication for 4 days prior to and during measurements (MED-HYP), in 9 untreated hypertensive men (HYP) and in 10 age-matched normotensive men before and after HIIT. At baseline, HYP and MED-HYP had lower mitral valve E/A ratio (MED-HYP, 0.86 ± 0.2; HYP, 0.99 ± 0.1; P < 0.05) compared with normotensive men (1.37 ± 0.4). The HIIT stroke volume in normotensive men only improved maximum oxygen uptake (change, 178 ± 239 mL O₂/min). The E/e' ratio (echocardiographic risk marker of cardiac events) increased (P < 0.05) with HIIT in MED-HYP, with no change in normotensive men and HYP. Men with treated and untreated essential hypertension display diminished cardiac adaptation and less improvement in cardiopulmonary fitness in response to HIIT compared with normotensive counterparts. Additionally, MED-HYP increased E/e' with HIIT, potentially raising the risk of primary cardiac events. Therefore, further research is required to assess the interactive effects of exercise training and antihypertensive treatment.

Reduced cardiorespiratory fitness is common among breast cancer survivors and, although traditionally attributed to cardiac dysfunction, might also be related to peripheral skeletal muscle abnormalities. We examined peak and submaximal plantar-flexion exercise and recovery kinetics for lower-leg oxygen uptake ( ${\dot{V}}_{O_2}$ ), blood flow and arteriovenous O₂ difference in 35 older, female long-term breast cancer survivors (age, 70 ± 5 years; 14 ± 6 years post-treatment) and 19 age- and sex-matched healthy control subjects using MRI. The calf intermuscular fat to skeletal muscle ratio was evaluated using fat- and water-separated MRI to quantify myosteatosis. No significant differences were found between groups for lower-leg ${\dot{V}}_{O_2}$ , blood flow or arteriovenous O₂ difference at peak or during submaximal plantar-flexion exercise. Recovery kinetics for these measures were similar between groups (all P > 0.05). No differences were found in calf muscle mass between breast cancer survivors and control subjects. A higher intermuscular fat to skeletal muscle ratio was significantly associated with reduced peak (cycle exercise) pulmonary ${\dot{V}}_{O_2}$ (r = -0.37, P = 0.01), lower plantar-flexion power output (r = -0.325, P = 0.012) and delayed muscle ${\dot{V}}_{O_2}$ recovery kinetics in both groups (r = -0.325, P = 0.015). Older, female long-term breast cancer survivors have comparable lower-limb skeletal muscle oxidative capacity to control subjects. However, myosteatosis represents a key determinant of exercise performance and recovery kinetics regardless of breast cancer history. Interventions targeting skeletal muscle quality might be effective in improving both submaximal and maximal exercise tolerance and recovery kinetics in older women with or without a breast cancer diagnosis.

The main sources of circulating erythropoietin (Epo) in the adult are kidney Norn cells, a recently identified interstitial cell type capable of becoming renal Epo-producing (REP) cells following a local decrease in tissue oxygenation. REP cells are restricted to small clusters in the corticomedullary border region, suggesting that their microenvironment is relevant for cell differentiation and/or proper regulation of Epo production. Possibly for the same reason, REP cells cease to produce Epo in injured kidneys, which is rapidly reverted by stabilizers of the hypoxia-inducible factor (HIF). To shed new light on the mechanisms governing Epo production, we combined spatial transcriptomics, mRNA fluorescence in situ hybridization and sequential immunofluorescence, enabling the characterization of the immediate neighbourhood of active REP cells. Although in the hypoxic mouse kidney REP cells were closest to proximal tubule segments (S) S1 to S2/3 and endothelial cells, Epo was reinduced by HIF stabilizers in injured kidneys in the vicinity of damaged proximal tubule cells that expressed high levels of injury markers. In contrast, the Norn and endothelial cell profiles remained normal. The REP cell microenvironment switched from pathways involved in energy metabolism in hypoxic conditions to inflammatory and fibrotic pathways in injury conditions. In summary, these data demonstrate that in the diseased kidney HIF stabilizers reinduce Epo expression in REP cells with a metabolically inactive proximal tubule neighbourhood, consistent with a causal role for tubular cells during the loss of Epo expression.

The aim of this work was to assess the effect of heat exposure on cardiorespiratory and haematological responses during de-training and re-training. Nineteen men (33.8 ± 2.7 years; 182 ± 5.7 cm, 84.4 ± 9.3 kg) completed 4 weeks of pre-training followed by heat exposure (HEAT; n = 9) or control (CON; n = 10). Both groups then de-trained for 2 weeks with lower-limb immobilization followed by 2 weeks of re-training. Cardiorespiratory fitness and total haemoglobin mass (Hb_mass) were measured at baseline (BASE), prior to (IMMO_pre) and following (IMMO_post) immobilization and after a 'return-to-sport' (RTS_post) training phase. Compared with IMMO_pre, ${\dot{V}}_{O_2}$ at the gas exchange threshold (GET) was reduced (d = -0.53; P < 0.005) at IMMO_post, whereas maximal oxygen uptake ( ${\dot{V}}_{O_2\max }$ ) did not change significantly (d = 0.14; P = 0.07). The reduction in GET ${\dot{V}}_{O_2}$ was more pronounced for HEAT than CON (d = -0.77; P = 0.001). At IMMO_post, GET and peak power output were lower than IMMO_pre (d = -1.4, P < 0.005 and d = 0.43, P = 0.01, respectively), however there was no difference between groups. At RTS_post, the ${\dot{V}}_{O_2}$ at GET increased again in both groups yet remained lower than IMMO_pre although the reduction in HEAT (d = -0.42; P = 0.43) was less than CON (d = -0.8; P = 0.05). At RTS_post, HEAT fully recovered GET power losses compared to IMMO_post (d = 1.1; P = 0.001), while CON only showed a trivial change (d = 0.07; P = 0.1). No significant changes were observed in Hb_mass, haematocrit or plasma volume throughout the study (P ≥ 0.763). Heat exposure did not attenuate a decline in cardiorespiratory fitness during immobilization-induced de-training, but could potentiate its recovery upon re-commencement of training.

We examined the impact of moderate hypoxia (HYPO) on muscle activation during incremental exercise matched for both absolute and equivalent relative intensity. Fifteen active subjects (10 males, 5 females) completed two ramp incremental test and two step tests in normoxia (NORM; $F_{i{O}_2}$  = 0.209) and HYPO ( $F_{i{O}_2}$ ≈ 0.135) in counterbalanced order. The respiratory compensation point (RCP) determined from ramp testing was used to normalize relative intensity during step testing, which included a final stage to task failure (TF) above RCP. Electromyography (EMG) was recorded for rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM), and normalized to a pre-test maximal sprint effort. Linear mixed modelling was used to examine fixed effects of condition (NORM, HYPO) and intensity (absolute, relative) on EMG activity. During the ramp test, HYPO significantly reduced ${\dot{V}}_{O_2\mathrm{peak}}$ (∼13%), PPO (∼15%), and power at RCP (∼16%). EMG breakpoints occurred at lower absolute intensity in HYPO for RF and VL. When matched for relative intensity, muscle activity was lower in HYPO for VM and VL, but not RF. EMG activity at TF revealed a similar pattern whereby a strong association to absolute power was present regardless of test protocol or $F_{i{O}_2}$ . These results suggest that altered relative metabolic stress has a negligible impact on muscle activation at work rates below the RCP. For exercise in the severe domain our data aligns with the theory that muscle activation is not critically regulated to a given level at TF, but appears to be task-specific and independent of oxygen availability.

Cathelicidins are evolutionarily conserved host defence peptides known for their dual antimicrobial and immunomodulatory functions. Among them, LL-37 in humans and CRAMP in rodents have emerged as crucial regulators of both mucosal immunity and CNS inflammation. This review explores the emerging evidence that positions cathelicidins as key modulators of the gut-brain axis, a bidirectional communication network increasingly implicated in neuroinflammatory and neurodegenerative disorders. Drawing on a diverse body of animal and human research, we examine the multifaceted roles of cathelicidin in maintaining intestinal barrier integrity, shaping microbiota composition and regulating innate immune signalling. Particular attention is paid to how gut-derived metabolites, such as short-chain fatty acids and vitamin D, influence cathelicidin expression, with downstream consequences for both gastrointestinal and neural health. In the CNS, cathelicidin exhibits context-dependent effects, acting as a neuroprotective modulator when derived from neurons, but exacerbating glial-mediated inflammation when sourced from peripheral immune cells. This functional dichotomy underscores the importance of cellular origin, concentration and microenvironmental cues. Furthermore, we delineate how cathelicidin facilitates crosstalk between peripheral and central compartments, serving as both a local effector and a systemic messenger. Collectively, these insights support a reconceptualization of cathelicidin not merely as a passive antimicrobial peptide, but as an active molecular bridge between mucosal immunity and neuroinflammation, with promising implications for diagnostics and therapeutics targeting dysfunction of the gut-brain axis.

Obesity (BMI ≥ 30 kg/m²) reduces skeletal muscle quality and impairs the myogenic response to muscle damage. The present study investigated if differences exist in myotubes from individuals with (OB) or without (LN) obesity incubated in control (bovine serum albumin [BSA]) or obesogenic (Ob) medium, at baseline or in response to cardiotoxin (CTX)-induced damage and recovery. Differentiated, primary human myotubes from LN and OB donors were cultured in control (BSA-DM) or (Ob-DM) (250 µM palmitate, 250 µM oleate, 100 nM insulin, and 2.5 ng/mL tumour necrosis factor) differentiation medium (DM) for 48 h and treated with 1.0 µM CTX or vehicle control for 1 h (immediately post [IP]). Myotubes recovered in Ob (Ob-GM) or BSA (BSA-GM) growth medium (GM) for 3 days (3D). At baseline, myotubes (LN and OB) incubated in Ob-DM had 5% lower fusion index (FI) and nuclei/tube than BSA-DM. At IP post-CTX, there were no differences in FI or membrane integrity (lactate dehydrogenase), but the reduction in cell viability was greater in OB than LN myotubes and greater in myotubes (LN and OB) incubated in Ob-DM than BSA-DM. At 3D post-CTX, total nuclei, FI, and nuclei/tube were ∼15% lower in myotubes (LN and OB) incubated in Ob-GM than BSA-GM. Expressed as recovery (3D-IP) post-CTX, Ob-GM lowered total nuclei and FI in myotubes without differences between LN and OB. In human myotubes, impaired formation and recovery following damage in obesity appear primarily due to the obesogenic environment rather than inherent, individual differences.

Current literature on the metabolic effects of long-distance hiking is limited to case studies with discrepant findings, and no prior studies have examined the role of diet in shaping these outcomes. In this study, we investigated changes in lipid profiles and dietary factors among 12 participants who completed the Colorado Trail. Blood lipid measures [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, total cholesterol and triglycerides] were obtained pre- and post-trail after a 12 h fast using the Lysun Blood Lipid Analyzer. Dietary intake was assessed pre- and on-trail using a validated multiple-pass 24 h recall. Student's paired t-tests evaluated metabolic changes, and regression analyses assessed associations between lipid changes and dietary factors. No lipid exhibited a statistically significant change at the α = 0.05 threshold. However, LDL-C decreased by 17 mg/dL (P = 0.066), suggestive of a biologically meaningful reduction, given the small sample size. Among 81 dietary variables, LDL-C reduction was significantly associated with decreased intake of added sugars (P = 0.030) and ultra-processed foods (P = 0.039) and with increased intake of minimally processed foods (P = 0.044), vitamin C (P = 0.048) and vitamin K (P = 0.047) during hiking. These findings suggest that long-distance hiking might be associated with lower LDL-C and that diet quality, particularly food processing level, might be correlated with this trend. This study is the first to link dietary shifts systematically to metabolic outcomes in thru-hiking, providing hypothesis-generating insights into the physiological adaptations to prolonged physical exertion and the potential for dietary modulation of lipid metabolism.