American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Defining human thermoregulation limits: a critical evaluation of predictive models using healthy young adults.","authors":"Faming Wang, Huijuan Xu, Tze-Huan Lei, Yi Xu, Haojian Wang, Lijuan Wang","doi":"10.1152/ajpregu.00108.2025","DOIUrl":"10.1152/ajpregu.00108.2025","url":null,"abstract":"<p><p>The core temperature inflection point (CTIP) method (also known as humidity-ramp protocol) and biophysical modeling are widely used to determine human thermoregulation limits, yet their validity under prolonged heat exposure remains unverified. This study evaluated the predictive accuracy by exposing 36 healthy young adults (20 males and 16 females) to five counterbalanced 8-h indoor heat trials in a controlled chamber (36°C/74.5%RH, 40°C/55.0%RH, 44°C/29.2%RH, 47°C/35.6%RH, and 50°C/24.5%RH). These conditions were selected based on prior CTIP and biophysical model predictions of human thermoregulation limits. Participants engaged in sedentary office tasks (1.29-1.67 METs), wore standardized summer clothing (0.39-0.40 clo), and had ad libitum access to an electrolyte drink, with a 500-kcal sandwich provided at midday. Rectal temperature (<i>T</i>_rec) was continuously monitored. Contrary to model predictions, all five conditions remained compensable (<i>T</i>_rec rise rate ≤ 0.1°C/h), with mean peak <i>T</i>_rec well below heatstroke thresholds (38.2 ± 0.4°C). At 44°C/29.2%RH, females exhibited significantly lower <i>T</i>_rec than males (<i>P</i> < 0.05); however, no sex differences in steady-state <i>T</i>_rec responses were observed across other conditions (all <i>P</i> > 0.10). All exposures were compensable, aligning with the broader literature indicating minimal sex-based variability under such conditions. Collectively, CTIP and biophysical models substantially underestimated human thermoregulation limits, leading to overpredicted heat risk across all trials. These findings challenge the reliability of current predictive methods, suggesting human tolerance may exceed existing estimates. Refining these models is essential for improving heat risk assessment and informing public and occupational health guidelines in a warming climate.<b>NEW & NOTEWORTHY</b> This study reveals that widely used methods-core temperature inflection point and biophysical models-substantially underestimate human thermoregulation limits during prolonged heat exposure. Despite predictions of uncompensable heat stress, all five 8-h trials remained compensable, with core temperatures well below critical thresholds. These findings challenge the accuracy of current predictive tools and highlight the need to refine models to better assess heat risk in real-world, prolonged exposure scenarios.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R524-R533"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the enterohepatic paradigm in sleeve gastrectomy: bile acids lead, microbiome follows.","authors":"Gopala Koneru, Lama Noureddine, Mohamad Mokadem","doi":"10.1152/ajpregu.00204.2025","DOIUrl":"10.1152/ajpregu.00204.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R586-R588"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perfusion-dependent modulation of muscle contractility: an alternative perspective on fatigue and blood flow.","authors":"Simon Green","doi":"10.1152/ajpregu.00162.2025","DOIUrl":"10.1152/ajpregu.00162.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R550-R554"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific systemic metabolic predictors of resistance to calorie restriction-induced weight loss in obese diversity outbred mice.","authors":"Evan M Paules, Melissa VerHague, Anju A Lulla, Katie A Meyer, Michael F Coleman, Jody Albright, Brian J Bennett, Kari E North, Annie Green Howard, Penny Gordon-Larsen, Isis Trujillo-Gonzalez, John E French, Stephen D Hursting","doi":"10.1152/ajpregu.00220.2024","DOIUrl":"10.1152/ajpregu.00220.2024","url":null,"abstract":"<p><p>Calorie restriction (CR) is a well-established weight loss strategy, albeit with variation in response. Using genetically heterogeneous mice, we sought to identify metabolic predictors of resistance to CR-induced weight loss. Diversity outbred (DO) mice (150 males and 150 females) were fed a high-fat diet for 12 wk to generate diet-induced obesity (DIO), then underwent CR for 8 wk. Body weight and composition, blood glucose, and plasma levels of nine metabolic hormones were assessed at baseline, following DIO, and following CR. In response to each dietary intervention, the mice displayed substantial heterogeneity across all outcomes, often with sexual dimorphism. Among the metabolic markers, leptin changed the most in response to each dietary intervention. Logistic regression found that resistance to CR-induced weight loss in obese mice was associated with lower glucose levels in males, and with lower levels of insulin, resistin, homeostatic model assessment for insulin resistance (HOMA-IR), and plasminogen activator inhibitor-1 and higher levels of ghrelin in females. Moreover, lower leptin levels predicted resistance to CR-induced weight loss in obese mice, regardless of sex. These preclinical findings provide proof-of-principle that the genetic and phenotypic heterogeneity of DO mice can be leveraged to identify mechanistic predictors that may enhance the personalization of weight loss interventions.<b>NEW & NOTEWORTHY</b> Using a population of obese diversity outbred (DO) mice, we interrogated plasma predictors of resistance to calorie restriction-induced weight loss in nonresponders versus responders to the diet intervention. Lower leptin levels significantly predicted resistance in both sexes. Sexually dimorphic predictors included lower levels of glucose in males and insulin, resistin, and plasminogen activator inhibitor-1 (PAI-1) in females. Hence, genetically and phenotypically heterogeneous diversity outbred mice may be useful for identifying metabolic predictors for personalizing weight loss interventions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R576-R585"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating endothelial extracellular vesicles progressively increase with age and are associated with endothelial vasodilator dysfunction.","authors":"Christian S DeSouza, Kelly A Stockelman, Jamie G Hijmans, Tyler D Bammert, Grace M Lincenburg, Jared J Greiner, Vinicius P Garcia, Brian L Stauffer, Christopher A DeSouza","doi":"10.1152/ajpregu.00146.2025","DOIUrl":"10.1152/ajpregu.00146.2025","url":null,"abstract":"<p><p>Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), have been linked to the development and progression of endothelial dysfunction and CVD. The purpose of this study was to determine <i>1</i>) if circulating EMV levels increase with age, independent of other cardiometabolic risk factors; and if so, <i>2</i>) whether circulating EMVs are associated with age-related endothelial vasodilator dysfunction. Forty healthy, nonobese, normotensive, sedentary males were studied: 12 young (age: 27 ± 5 yr), 14 midlife (51 ± 5 yr), and 14 older (67 ± 5 yr). EMV identification (CD31⁺/42b^-) and concentration in peripheral blood were determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine and sodium nitroprusside. Circulating EMV levels were significantly and progressively higher across the young, midlife, and older groups (54 ± 14 vs. 101 ± 30 vs. 132 ± 54 EMV/µL, respectively). FBF response to acetylcholine was significantly lower (∼30%) in the midlife (4.5 ± 0.8 to 13.5 ± 3.3 mL/100 mL tissue/min) and older (4.2 ± 1.0 to 11.5 ± 2.8 mL/100 mL tissue/min) vs. young (from 5.2 ± 1.1 to 17.2 ± 4.9 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (<i>r</i> = 0.69; <i>P</i> < 0.001) and inversely associated with endothelial vasodilation (peak FBF to acetylcholine: <i>r</i> = -0.51; and total FBF to acetylcholine: <i>r</i> = -0.48; <i>P</i> = 0.02). Aging, independent of other cardiometabolic risk factors, is associated with progressively elevated circulating levels of EMVs in healthy males. Circulating EMVs may serve as a biomarker of, and potential contributor to, age-related endothelial dysfunction and vascular disease risk.<b>NEW & NOTEWORTHY</b> Aging is associated with progressive decline in endothelium-dependent vasodilation. Mechanisms underlying this decline in endothelial function are not fully understood. Circulating endothelial cell-derived extracellular vesicles (EMVs) have been linked to endothelial dysfunction. The results of the study demonstrate that circulating EMVs increase with age in healthy males and are associated with endothelial vasodilator dysfunction. Circulating EMVs represent a novel systemic biomarker, and potential mediator, of age-related decline in endothelium-dependent vasodilation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R509-R514"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of foot and neck cooling on autophagy and cellular stress responses in peripheral blood mononuclear cells from older adults exposed to extreme heat.","authors":"James J McCormick, Kelli E King, Emma R McCourt, Robert D Meade, Glen P Kenny","doi":"10.1152/ajpregu.00110.2025","DOIUrl":"10.1152/ajpregu.00110.2025","url":null,"abstract":"<p><p>With rising average global temperatures, extreme heat events are becoming more frequent and intense, placing heat-vulnerable older adults at an elevated risk of mortality and morbidity. We recently showed that a brief 2 h access to air-conditioning during a simulated heatwave confers cytoprotective benefits in older adults; however, air-conditioning is inaccessible to many. Although foot immersion and neck cooling have been proposed as alternative cooling strategies, their effects on cellular stress are unclear. We evaluated cellular responses (autophagy, apoptosis, acute inflammation, and heat shock proteins) in peripheral blood mononuclear cells from 17 participants (9 females, median age: 72 [IQR, 69-74] yr) who completed three, 6-h heat exposures at 38°C (35% relative humidity) with either no-cooling (control), submersion of the feet (mid-calf) in 20°C water for 40-min each hour or foot immersion with a cool wet towel (20°C) around the neck. Core (rectal) temperature was measured continuously. Western blot analysis was used to assess changes in protein responses at baseline and end exposure. Despite similar elevations in core temperature between conditions, p62 concentrations were elevated in the control compared with both foot immersion with [mean difference: 0.4 relative quantity (RQ); <i>P</i> = 0.046] and without (0.6 RQ; <i>P</i> = 0.026) neck cooling. Furthermore, HSP70 concentrations were elevated in control compared with foot immersion (0.7 RQ; <i>P</i> = 0.030). No changes between conditions were observed for apoptotic or inflammatory proteins. Although foot immersion with or without neck cooling had minimal impact on core temperature, these strategies may improve autophagic responses in older adults when exposed to extreme heat.<b>NEW & NOTEWORTHY</b> As the incidence and severity of heatwaves continue to rise, there is an urgent need to develop accessible and sustainable heat-alleviation strategies. We evaluated the use of foot immersion in cool water with or without the addition of a damp towel around the neck on cellular stress responses in older adults exposed to extreme heat. Although neither cooling intervention reduced elevations in core temperature, both cooling strategies may improve autophagic responses in older adults.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R515-R523"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated muscle protein synthesis during disuse and rehabilitation in late-midlife adults.","authors":"Sean P Kilroe, Zachary D Von Ruff, Hanna Kalenta, Vladislav Bugay, Emily J Arentson-Lantz, Andrew J Murton, Victoria G Rontoyannni, Doaa Reda Abdelrahman, Elena Volpi, Douglas Paddon-Jones, Blake B Rasmussen","doi":"10.1152/ajpregu.00072.2025","DOIUrl":"10.1152/ajpregu.00072.2025","url":null,"abstract":"<p><p>The purpose of this study was to investigate the sex-specific differences in how late-midlife adults respond to short-term disuse and rehabilitation. Sixteen late-midlife adults, who were free of overt disease (8 males: 58 ± 2 yr, BMI 29.4 ± 0.8 kg·m^-2; 8 postmenopausal females: 56 ± 2 yr, BMI 29.1 ± 1.1 kg·m^-2) underwent 7 days of unilateral lower limb suspension (ULLS), followed by 7 days of rehabilitation. Vastus lateralis muscle biopsies were collected before and following ULLS [in both control (CON) and immobilized (IMM) legs] and in the IMM leg post-rehabilitation. We applied deuterium oxide to measure muscle protein synthesis (MPS), immunoblotting to assess mTORC1 signaling, and assessed changes in muscle fiber cross-sectional area (CSA) and leg strength. MPS was 17.8 ± 14.6 and 32.7 ± 10.9% lower in the IMM compared with the CON leg in males (<i>P</i> = 0.32) and females (<i>P</i> < 0.05), respectively, during immobilization. MPS was 27.5 ± 24.5 and 9.7 ± 38.9% higher in the IMM leg during the rehab compared with during the IMM phase in the males and females, respectively (<i>P</i> > 0.05). Leg extension one repetition maximum declined by 24.2 ± 2.4 and 17.1 ± 2.1% in males and females, respectively, after IMM (both <i>P</i> < 0.01), in the IMM leg with no change in the CON leg (<i>P</i> > 0.05). Our data show that late-midlife males and females experience similar reductions in MPS and muscle fiber CSA. Seven days of resistance exercise rehabilitation partially reverses the decline in muscle strength, CSA, and MPS, but longer rehabilitation periods are required for full recovery in late-midlife adults.<b>NEW & NOTEWORTHY</b> This study provides novel data on the average rate of muscle protein synthesis during 7 days of disuse and 7 days of rehabilitation in late-midlife adults. Both sexes experienced a similar reduction in muscle protein synthesis, strength, and fiber cross-sectional area during disuse. Seven days of resistance exercise rehabilitation partially reverses the disuse-induced decline in muscle protein synthesis, strength, and fiber size; however, longer periods of rehabilitation are required for full recovery.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R537-R549"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turning up the gain without resistance: uncoupling of sympathetic transduction and vascular conductance following exercise.","authors":"Eloisa Herrera-Ospina, Bruno T Roseguini, Igor A Fernandes","doi":"10.1152/ajpregu.00186.2025","DOIUrl":"10.1152/ajpregu.00186.2025","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R534-R536"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular origin of body temperature in homeothermic species.","authors":"Gerhard M Artmann, Oliver H Weiergräber, Samar Damiati, Ipek Seda Firat, Aysegül T Artmann","doi":"10.1152/ajpregu.00236.2024","DOIUrl":"10.1152/ajpregu.00236.2024","url":null,"abstract":"<p><p>We propose the interfacial water quantum-transition (IWQ) model as a novel paradigm explaining temperature-dependent structural and functional transitions (discontinuities) observed in proteins. The central postulate states that experimentally measured critical temperatures, T_C, are related to physical reference temperatures, T_W, defined by rotational quantum transitions of temporarily free water molecules in the protein-water interface. Applicability of this concept is demonstrated with transitions observed in two disparate model systems, viz., hemoglobin and thermosensitive transient receptor potential (TRP) channels. We propose that the same mechanism underlies the definition of basal body temperatures in homeotherms, the reference temperature for humans being T_W = 36.32°C. Specifically, we demonstrate that the body temperatures of both human and chicken (representing the two classes of homeothermic vertebrates) not only coincide with quantum-transition reference temperatures but are also related to pronounced transitions in hemoglobin oxygen saturation. This suggests that the evolution of body temperatures in different homeothermic species might involve an interplay between critical parameters of oxygen supply on the one hand and quantum-physical rotational transition temperatures of water on the other. Casting the IWQ model concept into a concise formula: Proteins sense and water sets critical physiological temperatures.<b>NEW & NOTEWORTHY</b> We propose the interfacial water quantum-transition (IWQ) model to explain how proteins respond to temperature changes through specific quantum transitions of water at the protein-water interface. This model links key functional temperatures, such as human body temperature, to these transitions. By examining proteins like hemoglobin and thermosensitive channels, the IWQ model reveals a fundamental connection between water behavior and biological temperature regulation, shedding light on evolutionary adaptations in humans and animals.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R555-R575"},"PeriodicalIF":2.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine organic anion increases with age and its effects on renal acid excretion vary with pKa.","authors":"Priya Meera Rawal, Yasin R Badawy, Elaine M Worcester, Fredric L Coe, Megan Prochaska","doi":"10.1152/ajpregu.00147.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00147.2025","url":null,"abstract":"<p><p>Findings of falling urine pH with age among stone formers have not been explained by changes in renal function or renal ammonia production with age. We collected and analyzed 245 urines from 190 stone forming subjects (95 male) and 55 normal subjects (18 male), to expand on our previous study using urine titration to explore whether urine organic anion (Uoa) contributes to acid load and rises with age. We stratified our previous titration protocol to include three pKa subranges: 2.70-3.60, 3.61-4.30, and 4.31-7.40, to measure effects of Uoa of differing pKa values on renal acid excretion. We found that Uoa behaves as a metabolic acid, and associates independently and positively with ammonia (<i>p</i> < 0.001). Uoa in pKa range 2.70-3.60 are the principal acid component, and rise with age (<i>p</i> < 0.001), while Uoa in pKa range 4.31-7.40 seem to reflect net alkali excretion when studied in a regression model with the kidney as a reporter organ. When factored per urine creatinine, we found significant age and sex effects of nearly all components of renal acid-base balance. Effects from subject type (stone former vs. normal) were minimal, though we are limited by the oldest tertile having few normals. As acid anions with pKa within 2.70-3.60 are used in the tricarboxylic acid cycle, markers of acid excretion may reflect mitochondrial abnormalities associated with aging.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}