Maartje Cox, Aaron Raman, Timothy Fairchild, John P Beilby, Bu B Yeap, Jeremy K Nicholson, Julien Wist, Jeremiah Peiffer, Nathan G Lawler
{"title":"Effects of short-term exercise on plasma metabolic and lipidomic profiles of individuals with type 2 diabetes.","authors":"Maartje Cox, Aaron Raman, Timothy Fairchild, John P Beilby, Bu B Yeap, Jeremy K Nicholson, Julien Wist, Jeremiah Peiffer, Nathan G Lawler","doi":"10.1113/EP092768","DOIUrl":"https://doi.org/10.1113/EP092768","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycaemia, with physical inactivity and excessive adiposity as predisposing factors. This clinical trial aimed to investigate the effects of an exercise intervention on the metabolome of T2DM participants, fasting and in response to an oral glucose tolerance test (OGTT) and an acute exercise stimulus. Thirteen people with T2DM (age 51 ± 7 years; body mass index 32.7 ± 4.9 kg/m<sup>2</sup>) completed 45 min of moderate-intensity treadmill exercise on 12 days consecutively. Blood samples were collected before and after the first and last training sessions and during a pre- and postintervention OGTT. Fasted blood samples were collected from 198 healthy control subjects and 208 people with T2DM from an independent cohort for comparison. Samples were analysed using high-resolution <sup>1</sup>H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. The exercise intervention did not induce a shift towards a healthier fasted metabolome in people living with T2DM. In response to consumption of a glucose bolus (OGTT), glycolysis-related metabolites increased and free fatty acids decreased, with no effect of the exercise intervention. In response to acute exercise, glucose and amino acids decreased and free fatty acids increased, with similar responses on the last day of training as on the first day, indicating no effect of the intervention. The clinical trial was registered prospectively in the Australian New Zealand Clinical Trials Registry ACTRN12617000286347 on 24 February 2017.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alex A M Gould, Neil P Walsh, Michael J Tipton, Michael J Zurawlew, Omar Tayari, Carol House, Simon K Delves, Samuel C Robson, Janis J Shute, Joy E M Watts, Andrew J Roberts, Alex J Rawcliffe, Megan R Robinson, Jo Corbett
{"title":"Faecal microbiome, gastrointestinal integrity, inflammation and thermoregulation in recent exertional heat illness patients and matched controls.","authors":"Alex A M Gould, Neil P Walsh, Michael J Tipton, Michael J Zurawlew, Omar Tayari, Carol House, Simon K Delves, Samuel C Robson, Janis J Shute, Joy E M Watts, Andrew J Roberts, Alex J Rawcliffe, Megan R Robinson, Jo Corbett","doi":"10.1113/EP092849","DOIUrl":"https://doi.org/10.1113/EP092849","url":null,"abstract":"<p><p>The gastrointestinal (GI) microbiota and GI barrier integrity are hypothesised to contribute to exertional heat illness (EHI) aetiology. We compared the faecal microbiome, GI barrier integrity, inflammation and thermoregulation of 29 recent (∼4 months) EHI patients (a group with elevated EHI risk) and 29 control individuals without prior EHI history, matched for variables influencing thermoregulation and GI microbiota. Participants completed an exercise heat tolerance assessment (HTA), with faecal microbiome assessed by 16S rRNA gene amplicon sequencing of stool samples and blood biomarkers of GI barrier integrity and inflammation measured pre- and post-HTA. With the exception of the Simpson index (patient = 0.97 ± 0.01 vs. control = 0.98 ± 0.00, P = 0.030), there were no between-groups differences in faecal microbiome composition (α-diversity, β-diversity, relative abundance, differential abundance), GI barrier integrity, inflammation or terminal thermoregulatory indices. Individuals were subsequently classified as heat tolerant (n = 46) or intolerant (n = 12) on the basis of the HTA. Heat intolerant individuals demonstrated lower sudomotor response (intolerant = 0.53 (0.17) vs. tolerant = 0.62 (0.20) L m<sup>-2</sup> h<sup>-1</sup>, P = 0.011) despite greater thermoregulatory strain (e.g., terminal T<sub>rec</sub>: intolerant = 39.20 ± 0.31 vs. tolerant = 38.80 ± 0.31°C, P < 0.001), lower Firmicutes:Bacteroidota ratio (intolerant = 3.7 (0.6) vs. tolerant = 4.5 (2.0), P = 0.019) and higher plasma [sCD14] (P = 0.014), but other aspects of faecal microbiome, GI integrity or inflammation did not differ from heat tolerant individuals. In conclusion, the faecal microbiome composition and the GI barrier integrity and inflammatory responses to exercise heat-stress showed limited differences between recent EHI patients and matched controls, or between individuals classified as heat intolerant or heat tolerant and are unlikely to explain elevated EHI risk in recent EHI patients, or heat intolerance.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Damian M Bailey, Vaughan G Macefield, David C Poole
{"title":"Physiology of nitrogen: A life or death matter.","authors":"Damian M Bailey, Vaughan G Macefield, David C Poole","doi":"10.1113/EP092946","DOIUrl":"10.1113/EP092946","url":null,"abstract":"<p><p>With each breath, four out of every five molecules we inspire are nitrogen (N<sub>2</sub>), since this gas constitutes ∼80% of the atmospheric air that surrounds us. Despite its abundance and unlike molecular oxygen, N<sub>2</sub> has traditionally held less appeal among physiologists given its lack of reactivity and corresponding inability to support combustion or life, rendering it metabolically nugatory. The controversial application of N<sub>2</sub> asphyxiation for the inhumane purposes of human execution of convicted criminals and assisted suicide of a terminally ill patient has thrust this important gas into the scientific and public spotlight, sparking widespread condemnation. In the current review, we take an opportunity to explore the molecular bases and clinical consequences linked to the Janus-faced physiology of N<sub>2</sub> to better explain its life-and-death qualities. We highlight the complex history that led to its discovery and the physio-geochemical evolution of Earth's uniquely N<sub>2</sub>-rich atmosphere, including intimate links with oxygen (O<sub>2</sub>), another life-and-death homonuclear diatomic gas that preceded aerobic respiration and the emergence of complex multicellular life. Diving deep into N<sub>2</sub>'s quantum state, we expose its unique physiochemical properties to better understand why this gas is metabolically inert and physiologically deadly when in excess and especially to the exclusion of O<sub>2</sub>. We apply this integrated physiological knowledge to further inform the controversial public debate and directly challenge the misconceived notion that N<sub>2</sub> gas asphyxiation offers a quick, indolent and dignified death for the inhumane purposes of human execution and assisted suicide.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ramona E Weber, Kiana M Schulze, Andrew G Horn, Tyler E McCoach, Zachary J White, K Sue Hageman, Stephanie E Hall, Peter Sandner, Brad J Behnke, Timothy I Musch, David C Poole
{"title":"Effects of soluble guanylyl cyclase stimulation on muscle oxygenation and exercise capacity in heart failure with mildly reduced ejection fraction.","authors":"Ramona E Weber, Kiana M Schulze, Andrew G Horn, Tyler E McCoach, Zachary J White, K Sue Hageman, Stephanie E Hall, Peter Sandner, Brad J Behnke, Timothy I Musch, David C Poole","doi":"10.1113/EP092756","DOIUrl":"10.1113/EP092756","url":null,"abstract":"<p><p>Heart failure (HF) with a mildly reduced ejection fraction (HFmrEF; 40%-49%) is present in ≤25% of HF patients. Therapeutic treatment options for HFmrEF-associated exercise intolerance are limited. Nitric oxide (NO)-independent stimulation of soluble guanylyl cyclase to improve peripheral vasodilatation offers a novel approach to enhance skeletal muscle oxygenation (interstitial pressure of O<sub>2</sub>) and exercise capacity. We tested the hypotheses that the soluble guanylyl cyclase stimulator BAY 41-2272 (BAY41) would increase exercise tolerance, skeletal muscle interstitial pressure of O<sub>2</sub> during contractions and NO sensitivity in rats with HFmrEF. Healthy Sprague-Dawley rats (n = 20) and rats with experimentally induced HFmrEF (n = 25) (3-4 months old) were used for this investigation. HFmrEF was confirmed via echocardiography, and rats were randomized and treated with 1.0 mg/kg of BAY41 or vehicle for 2 weeks, followed by exercise testing and spinotrapezius muscle phosphorescence quenching measurements during 1 Hz contractions. The HFmrEF rats had a lower exercise capacity than healthy rats (834 ± 169 vs. 1138 ± 214 s; p < 0.001). BAY41 increased exercise capacity (1158 ± 223 s; p = 0.006) and muscle oxygenation index (1461 ± 427 vs. 1108 ± 239 mmHg·s; p = 0.047) during 1 Hz contractions versus HFmrEF vehicle control rats. Sodium nitroprusside superfusion elicited a faster response time in BAY41-treated HFmrEF rats versus vehicle-treated control animals (150 ± 58 vs. 220 ± 50 s; p = 0.022). After sodium nitroprusside superfusion, BAY41-treated HFmrEF rats had a significantly elevated muscle oxygenation index during steady-state contractions versus vehicle-treated control animals (3104 ± 703 vs. 2365 ± 682 mmHg·s; p = 0.027). These data suggest that stimulation with soluble guanylyl cyclase can improve skeletal muscle oxygenation and increase the exercise capacity in HFmrEF rats, potentially via enhanced vascular smooth muscle NO sensitivity.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From fatigue to physiology: Submaximal 2-day cardiopulmonary exercise test and emerging standards in long COVID.","authors":"Michael G Risbano","doi":"10.1113/EP092958","DOIUrl":"https://doi.org/10.1113/EP092958","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Afaf Mehiou, Anca Lucau-Danila, Zachee L E Akissi, Chaimae Alla, Nourelhouda Bouanani, Abdelkhaleq Legssyer, Jean-Louis Hilbert, Sevser Sahpaz, Abderrahim Ziyyat
{"title":"Reply to: Galloyl-bis-hexahydroxydiphenoyl glucose and endothelial remodelling: Nutrigenomic insights into blackberry's superior vasorelaxant efficacy over mugwort.","authors":"Afaf Mehiou, Anca Lucau-Danila, Zachee L E Akissi, Chaimae Alla, Nourelhouda Bouanani, Abdelkhaleq Legssyer, Jean-Louis Hilbert, Sevser Sahpaz, Abderrahim Ziyyat","doi":"10.1113/EP092989","DOIUrl":"https://doi.org/10.1113/EP092989","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increases in skin perfusion and blood oxygen in the non-exercising human limbs during exercise in the heat: Implications for control of circulation.","authors":"Steven J Trangmar, José González-Alonso","doi":"10.1113/EP092742","DOIUrl":"https://doi.org/10.1113/EP092742","url":null,"abstract":"<p><p>Blood flow in the inactive limb tissues and skin is widely thought to decline during incremental exercise to exhaustion due to augmented sympathoadrenal vasoconstrictor activity, but direct evidence to support this view is lacking. Here, we investigated the inactive-forearm haemodynamic ( <math> <semantics> <msub><mover><mi>Q</mi> <mo>̇</mo></mover> <mi>forearm</mi></msub> <annotation>${dot{Q}}_{mathrm{forearm}}$</annotation></semantics> </math> ) and oxygenation responses to a range of two-leg exercise intensities and durations in the heat. Blood oxygen and flow were measured in the forearm tissue and skin of endurance-trained males during three incremental cycling exercise tests, with tests 1 and 2 separated by a 2 h bout of moderate constant load cycling exercise, all performed in the heat (35°C, 50% relative humidity, with fan cooling). In incremental exercise tests 1 and 3, <math> <semantics> <msub><mover><mi>Q</mi> <mo>̇</mo></mover> <mi>forearm</mi></msub> <annotation>${dot{Q}}_{mathrm{forearm}}$</annotation></semantics> </math> was stable from rest to ∼40% W<sub>peak</sub>, before increasing by ∼118% at 80% W<sub>peak</sub> (P <0.001). Correspondingly, forearm skin arterio-venous oxygen difference (a-vO<sub>2</sub> diff) decreased by ∼62% at 80% W<sub>peak</sub> (P = 0.043), remaining reduced through to W<sub>peak</sub>. Concomitantly, forearm skin blood flow more than doubled, while forearm deep tissue O<sub>2</sub> saturation decreased. When incremental exercise started shortly after constant load exercise (test 2), <math> <semantics> <msub><mover><mi>Q</mi> <mo>̇</mo></mover> <mi>forearm</mi></msub> <annotation>${dot{Q}}_{mathrm{forearm}}$</annotation></semantics> </math> was 2- to 3-fold higher than during tests 1 and 3, whereas skin a-vO<sub>2</sub> diff was suppressed to a low level. Similar changes were observed during constant load exercise. In conclusion, skin perfusion increases during incremental exercise in the heat, concomitant to proportional reductions in oxygen extraction from the cutaneous circulation. Hence, contrary to the generally held view, skin perfusion remains elevated during maximal exercise and heat stress despite profound increases in sympathoadrenal activity.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The search for the ultra-elusive: Can computed cardiopulmonography enhance early detection of gas exchange abnormality?","authors":"Harry B Rossiter, Yannick Molgat-Seon","doi":"10.1113/EP092925","DOIUrl":"https://doi.org/10.1113/EP092925","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exercise modality-dependent mitochondrial respiratory capacity in satellite cells and conditioned serum-induced responses in cultured myotubes.","authors":"Takanaga Shirai, Hayato Shinkai, Riku Tanimura, Kazuki Uemichi, Shunsuke Sugiyama, Kohei Takeda, Yu Kitaoka, Tohru Takemasa","doi":"10.1113/EP092922","DOIUrl":"https://doi.org/10.1113/EP092922","url":null,"abstract":"<p><p>Exercise-induced mitochondrial adaptations contribute to muscle function and metabolic health. We aimed to investigate the association of moderate-intensity swimming (MOD) and high-intensity interval training (HIIT) with mitochondrial function in skeletal muscle cells treated with exercise-conditioned serum. Male ICR mice (7-8 weeks old) were assigned to the Sedentary, MOD or HIIT group. The MOD group underwent five sessions of 60 min. The HIIT group performed weighted high-intensity swimming intervals. This study assessed mitochondrial enzyme activity in the plantaris muscle, mitochondrial respiratory capacity in isolated satellite cells, and mitochondrial function in C2C12 myotubes treated with exercise-derived serum. Serum was obtained immediately and 24 h postexercise to assess acute effects and chronic adaptations, respectively. The MOD and HIIT groups demonstrated significantly increased muscle citrate synthase and cytochrome c oxidase activities compared with the Sedentary group, but with no significant differences between the MOD and HIIT groups. Satellite cells exhibited higher basal respiration, ATP production and maximal respiratory capacity in the MOD group than in the Sedentary and HIIT groups. Acute serum notably improved maximal mitochondrial respiration in cultured C2C12 myotubes in the HIIT group, whereas serum from chronic training improved those parameters but demonstrated no modality-specific effects. MOD enhances mitochondrial respiratory function in satellite cells, probably owing to sustained aerobic metabolic signalling, whereas HIIT produces a potent but transient systemic response that acutely boosts mitochondrial function in muscle cells. The differential effects of exercise modalities emphasize the importance of timing and exercise modality in driving specific mitochondrial adaptations, thereby providing valuable insights for tailored exercise prescriptions for optimizing metabolic health.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}