{"title":"The skeletal muscle-adipose creatine metabolic axis: A novel paradigm for lipid metabolism reprogramming and obesity management.","authors":"Yuhui Su, Na Liu, Yang Liu, Yiqun Sun, Yike Jiao","doi":"10.1113/EP093049","DOIUrl":"https://doi.org/10.1113/EP093049","url":null,"abstract":"<p><p>The global prevalence of obesity and related metabolic disorders has spurred interdisciplinary research to develop new intervention strategies. Current research is increasingly focusing on the exercise-induced browning of white adipose tissue and the mechanisms by which it improves energy metabolism. Creatine, as the primary carrier of high-energy phosphate bonds within cells, is gaining attention for its role in the metabolic reprogramming of adipose tissue. This review aims to clarify the synergistic regulatory mechanisms between exercise and creatine metabolism, and introduces an innovative 'skeletal muscle-adipose creatine metabolic axis' model. Exercise may upregulate the expression of the creatine transporter in skeletal muscle by activating the AMP-activated protein kinase/peroxisome proliferator-activated receptor γ coactivator 1-α signalling pathway, enhancing phosphocreatine shuttle kinetics, and thereby increasing energy metabolism efficiency. Concurrently, exercise-induced exosomes or miRNAs from skeletal muscle may regulate the futile creatine cycle in adipose tissue and activate non-uncoupling protein 1-dependent thermogenic pathways, thus alleviating obesity conditions. This model not only reveals the multi-organ cross-talk mechanism mediated by exercise in lipid metabolism regulation but also provides a theoretical basis for creatine metabolism-targeted obesity interventions.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274261","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 physiology of survival: Space.","authors":"Damian M Bailey, Angelique van Ombergen","doi":"10.1113/EP093299","DOIUrl":"https://doi.org/10.1113/EP093299","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274202","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}
Marina Feeley, Tomoki Watada, Go Ito, Ai Shimada, Toru Sawai, Hideomi Nakata, Shingo Otsuki, Tadayoshi Miyamoto
{"title":"Time-course analysis of cerebral circulation and cardiorespiratory responses to acute central blood volume reduction in healthy young males.","authors":"Marina Feeley, Tomoki Watada, Go Ito, Ai Shimada, Toru Sawai, Hideomi Nakata, Shingo Otsuki, Tadayoshi Miyamoto","doi":"10.1113/EP092693","DOIUrl":"https://doi.org/10.1113/EP092693","url":null,"abstract":"<p><p>Central blood volume (CBV) reduction challenges circulatory and respiratory homeostasis, particularly during the initial compensatory phase (0-2 min), when rapid physiological adaptations occur. In this study, we examined dynamic cardiorespiratory responses to CBV reduction using lower-body negative pressure (LBNP) in 11 healthy young males. Participants completed three standardized 2 min LBNP trials at -45 mmHg, with respiratory variables assessed via flow measurement and breath-by-breath gas analysis, while cardiovascular parameters and cerebral blood flow were monitored using ECG, blood pressure and transcranial Doppler ultrasonography. During LBNP exposure, thoracic admittance, an indicator of CBV reduction, decreased by 13.4% (p < 0.001), indicating significant CBV reduction. Following rigorous statistical correction for multiple comparisons, time-course analysis revealed that mean blood pressure decreased temporarily during the initial phase (0-30 s), whereas heart rate increased progressively (16.4%, p < 0.001). End-tidal <math> <semantics><msub><mi>P</mi> <mrow><mi>C</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${P_{{mathrm{C}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> showed a consistent reduction (5.9%, p < 0.001), whereas minute ventilation and middle cerebral artery mean blood velocity showed no significant changes after statistical correction (-9.3% and -5.0%, respectively, p > 0.05). Exploratory correlation analysis revealed a significant negative correlation between mean blood pressure and tidal volume during the initial phase only (r = -0.78, p = 0.004). Cross-correlation analysis suggested temporal patterns between respiratory and cerebrovascular responses, with respiratory changes preceding cerebrovascular adjustments by 10-20 s. These findings, along with individual variability, suggest rapid cardiorespiratory and cerebrovascular interactions during orthostatic stress, demonstrating dynamic cardiovascular and respiratory responses with distinct temporal patterns that provide insights into physiological mechanisms maintaining homeostasis during gravitational stress.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274229","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}
Francesca De Faveri, Walter Marcotti, Federico Ceriani
{"title":"Spontaneous Ca<sup>2+</sup> signals in the developing mammalian cochlea of live mice under different anaesthetic regimes.","authors":"Francesca De Faveri, Walter Marcotti, Federico Ceriani","doi":"10.1113/EP093267","DOIUrl":"https://doi.org/10.1113/EP093267","url":null,"abstract":"<p><p>The pre-hearing mouse cochlea undergoes critical periods of spontaneous Ca<sup>2+</sup>-dependent activity that spreads across non-sensory supporting cells and inner hair cells (IHCs). These signals have been shown to regulate not only the refinement of neural circuits along the auditory pathway towards functional maturity, but also the maturation of the hair cells into sensory receptors. Although the origin and interplay of these Ca<sup>2+</sup> signals during cochlear development have recently been investigated in live mice, the impact of anaesthesia on in vivo functional measurements was not explored. Here, we investigate the effects of different anaesthetic regimes (ketamine and xylazine; 2.5% isoflurane; and 1.0%-1.5% isoflurane with the sedative acepromazine) that provided an effective unconsciousness to perform the surgery and Ca<sup>2+</sup>-imaging recordings from the intact cochlea of live mice. The IHCs, supporting cells and spiral ganglion neuron terminals onto the IHCs showed spontaneous Ca<sup>2+</sup>-dependent activity under all anaesthetic regimes, with a few significant differences observed between conditions. Calcium waves from supporting cells synchronized the activity of IHCs. Moreover, we found that the endocochlear potential, which is crucial for cochlear function, was unaffected by the different anaesthetics. However, low concentrations of isoflurane produced the most stable recordings of vital physiological signs in mice, including heart rate and breathing rate. Although all anaesthetic regimes tested appeared to be suitable for performing Ca<sup>2+</sup> imaging from the cochlea of pre-hearing live mice, a low concentration of isoflurane (1.0%-1.5%), combined with the pre-anaesthetic sedative acepromazine and oxygenation, represents the most suitable approach to maintain a stable and long-lasting depth of anaesthesia.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274283","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}
Sarah Thivent, J Alberto Neder, Anne-Catherine Bernard, Marie Coudurier, Michel Guinot, Frédéric Hérengt, Samuel Verges, Mathieu Marillier
{"title":"Locomotor muscle dysfunction and rehabilitative exercise training in fibrotic interstitial lung disease: Where are we at and where could we go?","authors":"Sarah Thivent, J Alberto Neder, Anne-Catherine Bernard, Marie Coudurier, Michel Guinot, Frédéric Hérengt, Samuel Verges, Mathieu Marillier","doi":"10.1113/EP091542","DOIUrl":"https://doi.org/10.1113/EP091542","url":null,"abstract":"<p><p>Exercise limitation is a cardinal feature of fibrotic interstitial lung disease arising from pulmonary gas exchange, respiratory mechanical and cardio-circulatory abnormalities. More recently, it has been recognized that impairment in locomotor muscle function (e.g., reduced muscle mass/strength or heightened fatigability) might also play a relevant contributory role. Exercise training as part of pulmonary rehabilitation is the most effective intervention to improve exercise tolerance, dyspnoea and quality of life in patients with fibrotic interstitial lung disease. Given that exercise training has modest effects on exertional ventilation, breathing pattern and respiratory muscle performance, improvement in locomotor muscle function is a key target for pulmonary rehabilitation in these patients. In the present narrative review, we initially discuss whether the locomotor muscles of patients might be exposed to negative risk factors. After offering corroboratory evidence on this matter (e.g., oxidative stress, inflammation, hypoxia, physical inactivity and medications), we outline their effects on skeletal muscle mass and functional properties. We finish by addressing the potentially beneficial effects of rehabilitative exercise training on these muscle-centred outcomes, providing perspectives to facilitate or optimize the muscle benefits derived from this intervention. This narrative review, therefore, provides an up-to-date outline of the rationale for rehabilitative approaches focusing on the locomotor muscles in this patient population.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243964","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":"No difference in mean middle cerebral artery blood velocity responses between lower- and upper-body unilateral resistance exercise in untrained individuals.","authors":"Stephanie Korad, Toby Mündel, Blake G Perry","doi":"10.1113/EP092859","DOIUrl":"https://doi.org/10.1113/EP092859","url":null,"abstract":"<p><p>Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure that are mirrored by middle cerebral artery blood velocity (MCAv). However, whether lower- or upper-body RE elicits a differential cerebrovascular response has not yet been examined. We investigated the cerebrovascular response to lower-body RE versus upper-body RE in 15 healthy untrained individuals (12 females and 3 males; mean ± SD; age 25 ± 6 years, height 179 ± 10 cm, weight 71 ± 15 kg and body mass index 24 ± 6 kg/m<sup>2</sup>). Participants completed four sets of 10 paced repetitions (15 repetitions/min) of unilateral leg-extension exercise and unilateral bicep-curl exercise at 60% of predicted one-repetition maximum (leg extension 30 ± 9 kg and bicep curl 7 ± 3 kg). Beat-to-beat blood pressure, bilateral MCAv and partial pressure of end-tidal carbon dioxide were measured throughout. Within-exercise mean arterial blood pressure (MAP) and mean MCAv were averaged across the set. Additionally, zenith, nadir and zenith-to-nadir difference in MAP and mean MCAv for each repetition were averaged across each set. Baseline measures preceding each set were not different for all dependent variables, with no significant interaction differences observed (all p > 0.161). The mean MCAv within exercise decreased across sets (set effect p < 0.001), but MAP did not (p = 0.071). No interaction effects were observed for any dependent variables (all p > 0.06), However, there was a zenith-to-nadir difference in mean MCAv (p = 0.008), although post hoc tests revealed no significant difference between exercises (all p > 0.078). There were no differences in the cerebrovascular and cardiovascular responses to lower- and upper-body RE, with similar sinusoidal fluctuations in MAP and MCAv<sub>mean</sub> present during both exercises.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238426","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}
Luca Mio, Giulio Pistorio, Atyieh Mohammadshirazi, Giuliano Taccola, Carmen Falcone
{"title":"Immediate cortical glial alterations following spinal cord injury: Evidence from a novel in vitro model.","authors":"Luca Mio, Giulio Pistorio, Atyieh Mohammadshirazi, Giuliano Taccola, Carmen Falcone","doi":"10.1113/EP092809","DOIUrl":"https://doi.org/10.1113/EP092809","url":null,"abstract":"<p><p>Spinal cord injury (SCI) triggers immediate and widespread pathophysiological changes not only at the site of impact but also beyond it, including alterations in remote cortical regions. Here, we report early astrocytic changes in the cerebral cortex following SCI at birth, identified using two specific glial markers in an innovative in vitro model of the entire central nervous system (CNS) isolated from neonatal rats. Immunohistochemical analyses revealed a significant reduction in cortical astrocyte density, first observed in the dorsomedial motor cortex (M1) within 25 min post-injury, followed by progressive changes in the ventrolateral somatosensory cortex (S1/S2) at 2 h post-injury. These findings indicate that SCI initiates a rapid and dynamic reorganization of cortical glial networks, shedding new light on astrocytic responses to spinal trauma.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238467","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}
Nicole N Eminhizer, Dena Lin, Alec Hanshew, Jackson Stewart, Steven Ball, Christa Lilly, Saina S Prabhu, Kate Karelina, Eric E Kelley, Randy W Bryner, Dharendra Thapa, Paul D Chantler
{"title":"Sex-dependent effects of a high-fat diet-induced obesity model on cerebrovascular health and brain metabolism.","authors":"Nicole N Eminhizer, Dena Lin, Alec Hanshew, Jackson Stewart, Steven Ball, Christa Lilly, Saina S Prabhu, Kate Karelina, Eric E Kelley, Randy W Bryner, Dharendra Thapa, Paul D Chantler","doi":"10.1113/EP093187","DOIUrl":"https://doi.org/10.1113/EP093187","url":null,"abstract":"<p><p>Mid-life obesity is a major risk factor for neurodegenerative diseases, with mitochondrial and cerebrovascular dysfunction considered key mediators. Lysine acetylation is a reversible post-translational modification that regulates several mitochondrial metabolic and biochemical processes. The present study investigated the sex-dependent effects of brain lysine acetylation and cerebrovascular and cognitive health in a high fat diet (HFD)-induced obesity mouse model. We hypothesize that a HFD will cause an increase in acetylation, dysregulating mitochondrial respiration, potentially due to the decline in overall cerebrovascular health. Six-month-old C57/Bl6 mice (M/F) were placed on a 60% HFD or normal chow (CON) for 4 months. Changes in cerebral blood flux (CBF), behavioural testing, glucose tolerance testing and body composition were tested. Brain lysates were probed for various substrate utilizations, bioenergetics proteins and lysine acetylation. A HFD resulted in global metabolic dysregulation, with a substantial increase in weight and fat mass, with a greater increase in female mice; however, no cognitive changes were noted. Additionally, unlike female mice, males demonstrated a decrease in CBF after a HFD. Brain lysine acetylation was decreased in male HFD mice but increased in female HFD mice. Similarly, acetylation levels of fatty acid oxidation protein (long-chain acyl-CoA dehydrogenase), glucose oxidation proteins (pyruvate dehydrogenase, pyruvate carboxylase) and electron transport chain complex I (NDUFB8) and IV (MTCO1) proteins were decreased in male and increased in female brains after a HFD. In summary, our findings propose lysine acetylation as a novel and potential regulatory mechanism that impacts vascular and metabolic function in the brain mitochondria in a sex-dependent manner.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225215","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}
Melissa Roths, Alyona Michael, Zachary J Schlader, Joshua T Selsby
{"title":"One day of environment-induced heat stress causes injury to the murine kidney.","authors":"Melissa Roths, Alyona Michael, Zachary J Schlader, Joshua T Selsby","doi":"10.1113/EP092975","DOIUrl":"https://doi.org/10.1113/EP092975","url":null,"abstract":"<p><p>Environment-induced heat stress (EIHS) results from sustained body temperature elevation owing to prolonged exposure to heat and humidity. We hypothesized that EIHS would cause kidney injury and cellular dysfunction. To test this hypothesis, female C57 mice were exposed to EIHS (n = 14; 37.6°C, 42.0% relative humidity) or thermoneutral (TN) conditions (n = 12; 31.2°C, 35.0% relative humidity) for 24 h. EIHS increased rectal temperature by 2.1°C (p < 0.001), decreased body mass by 10% (p = 0.036), decreased absolute kidney mass by 10% (p = 0.026), increased renal water content by 19% (p < 0.007) and increased blood urea nitrogen by 102% (p < 0.001) compared with TN. Histological analysis revealed that EIHS caused proximal tubule vacuolation (p = 0.001) and alterations in glomerular structure, supported by markers of lipid accumulation, tubular injury and inflammatory signalling. EIHS increased relative protein abundance of heat shock proteins 70 (48%, p = 0.002), 90 (37%, p = 0.001) and 60 (36%, p = 0.026), in addition to heat shock factor 1 (2-fold, p = 0.020) compared with TN. In addition, there was biochemical evidence of mitochondrial remodelling, increased autophagic flux and robust activation of endoplasmic reticulum stress in kidneys from EIHS mice compared with TN mice. Collectively, these data suggest that 24 h of EIHS is sufficient to cause histological injury and cellular dysfunction, which might undermine renal health and function.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206098","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}
Danny W Walmsley, Daniella Hurt, Abdulrahman A Dahesh, Kate Williams, Damian M Bailey
{"title":"Science that speaks: The public face of physiology.","authors":"Danny W Walmsley, Daniella Hurt, Abdulrahman A Dahesh, Kate Williams, Damian M Bailey","doi":"10.1113/EP093219","DOIUrl":"https://doi.org/10.1113/EP093219","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206067","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}