Acta Physiologica最新文献

{"title":"Inflammation-induced fever depends on prostaglandin E2 production by brain endothelial cells and EP3 receptors in the median preoptic nucleus of the hypothalamus","authors":"Anders Blomqvist","doi":"10.1111/apha.14238","DOIUrl":"10.1111/apha.14238","url":null,"abstract":"<p>I read with interest the editorial by Bai<span><sup>1</sup></span> on the paper by Yu et al.<span><sup>2</sup></span> on the role of caspase 11 in fever. However, I feel that the author ignores the absolutely critical role that prostaglandin (PG) E<sub>2</sub> production in brain endothelial cells has in generating fever, but rather seems to regard  it as an auxiliary mechanism. Although both peripheral and central cytokine production may contribute to fever, as suggested by the study by Yu et al.,<span><sup>2</sup></span> the critical mechanism is PGE<sub>2</sub> synthesis and its binding to EP<sub>3</sub> receptor expressing neurons in the median preoptic nucleus (MnPO) of the hypothalamus.<span><sup>3, 4</sup></span> If PGE<sub>2</sub> synthesis is blocked or EP<sub>3</sub> receptors are deleted in the MnPO, no fever occurs,<span><sup>5, 6</sup></span> even though there still is increased cytokine production in the periphery and in the brain.<span><sup>7</sup></span> The critical PGE<sub>2</sub> synthesis occurs in brain endothelial cells as shown by the absence of fever when the PGE<sub>2</sub> synthesizing enzymes cyclooxygenase-2 (Cox-2) and microsomal prostaglandin E synthase-1 (mPGES-1) are deleted from these cells.<span><sup>8</sup></span> Cox-2 and mPGES-1 are in turn induced by cytokine binding to receptors on the endothelial cells<span><sup>9-11</sup></span> (Figure 1). If these receptors, such as those for IL-1 and IL-6, or their downstream signaling molecules are selectively deleted from brain endothelial cells, the fever is suppressed.<span><sup>13-16</sup></span></p><p>It should also be pointed out that the evidence for the involvement of microglial cells in inflammation-induced sickness responses, and in particular in fever, is far from clear. Although it is well recognized that peripheral inflammation activates microglial cells,<span><sup>17</sup></span> the mechanism behind this activation is not fully understood. It is unlikely due to direct action of cytokines on the microglial cells, particularly when it comes to interleukin-1, which is a major pyrogen,<span><sup>18</sup></span> because if transport across the blood–brain barrier at all occurs in any significant amount, microglial cells express negligible levels of IL-1 receptors.<span><sup>19</sup></span> The critical IL-1 receptor-expressing cells for IL-1 activation of microglial cells are the endothelial cells, which via an as-yet-unidentified messenger molecule by a paracrine mechanism activate the microglial cells.<span><sup>20</sup></span></p><p>While it is generally assumed that various sickness symptoms and neuropsychiatric disorders are associated with activated microglia,<span><sup>21</sup></span> apart from a study demonstrating a role of striatal microglial cells in negative affect elicited by peripheral inflammation,<span><sup>22</sup></span> there is very little evidence for a causal relationship between these phenomena. It is not even clear which brain cel","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 12","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early growth response 1 exacerbates thoracic aortic aneurysm and dissection of mice by inducing the phenotypic switching of vascular smooth muscle cell through the activation of Krüppel-like factor 5","authors":"Xueyu Han,&nbsp;Shengnan Xu,&nbsp;Ke Hu,&nbsp;Yi Yu,&nbsp;Xiukun Wang,&nbsp;Chuan Qu,&nbsp;Bo Yang,&nbsp;Xin Liu","doi":"10.1111/apha.14237","DOIUrl":"10.1111/apha.14237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Vascular smooth muscle cell (VSMC) phenotypic switching has been reported to regulate vascular function and thoracic aortic aneurysm and dissection (TAAD) progression. Early growth response 1 (Egr1) is associated with the differentiation of VSMCs. However, the mechanisms through which Egr1 participates in the regulation of VSMCs and progression of TAAD remain unknown. This study aimed to investigate the role of Egr1 in the phenotypic switching of VSMCs and the development of TAAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type C57BL/6 and SMC-specific Egr1-knockout mice were used as experimental subjects and fed β-aminopropionitrile for 4 weeks to construct the TAAD model. Ultrasound and aortic staining were performed to examine the pathological features in thoracic aortic tissues. Transwell, wound healing, CCK8, and immunofluorescence assays detected the migration and proliferation of synthetic VSMCs. Egr1 was directly bound to the promoter of Krüppel-like factor 5 (KLF5) and promoted the expression of KLF5, which was validated by JASPAR database and dual-luciferase reporter assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Egr1 expression increased and was partially co-located with VSMCs in aortic tissues of mice with TAAD. SMC-specific Egr1 deficiency alleviated TAAD and inhibited the phenotypic switching of VSMC. Egr1 knockdown prevented the phenotypic switching of VSMCs and subsequently suppressed the migration and proliferation of synthetic VSMCs. The inhibitory effects of Egr1 deficiency on VSMCs were blunted once KLF5 was overexpressed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Egr1 aggravated the development of TAAD by promoting the phenotypic switching of VSMCs via enhancing the transcriptional activation of KLF5. These results suggest that inhibition of SMC-specific Egr1 expression is a promising therapy for TAAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 mediates mechanical signals in TRPV1-positive nociceptors in mice","authors":"Pa Reum Lee,&nbsp;Taewoong Ha,&nbsp;Hoon-Seong Choi,&nbsp;Seung Eun Lee,&nbsp;Chungho Kim,&nbsp;Gyu-Sang Hong","doi":"10.1111/apha.14236","DOIUrl":"10.1111/apha.14236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This investigation addresses Piezo1's expression and mechanistic role in dorsal root ganglion (DRG) neurons and delineates its participation in mechanical and inflammatory pain modulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed Piezo1's expression patterns in DRG neurons and utilized Piezo1-specific shRNA to modulate its activity. Electrophysiological assessments of mechanically activated (MA) currents in DRG neurons and behavioral analyses in mouse models of inflammatory pain were conducted to elucidate Piezo1's functional implications. Additionally, we investigated the excitability of TRPV1-expressing DRG neurons, particularly under inflammatory conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Piezo1 was preferentially expressed in DRG neurons co-expressing the TRPV1 nociceptor marker. Knockdown of Piezo1 attenuated intermediately adapting MA currents and lessened tactile pain hypersensitivity in models of inflammatory pain. Additionally, silencing Piezo1 modified the excitability of TRPV1-expressing neurons under inflammatory stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Piezo1 emerges as a key mediator in the transmission of mechanical and inflammatory pain, indicating its potential as a novel target for pain management therapies. Our finding not only advances the understanding of nociceptive signaling but also emphasizes the therapeutic potential of modulating Piezo1 in the treatment of pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The challenged urine bicarbonate excretion test in cystic fibrosis: A comprehensive analysis of urine acid/base parameters","authors":"Amalie Q. Rousing,&nbsp;Majbritt Jeppesen,&nbsp;Søren Jensen-Fangel,&nbsp;Jens Leipziger,&nbsp;Mads V. Sorensen,&nbsp;Peder Berg","doi":"10.1111/apha.14233","DOIUrl":"10.1111/apha.14233","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Renal excretion of excess HCO₃⁻ depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO₃⁻ excretion following oral NaHCO₃-loading may be a simple in vivo biomarker of CFTR function. In this study, we investigated changes in urine acid/base parameters following oral NaHCO₃-loading to comprehensively assess the physiological response to the test and evaluate HCO₃⁻ as the primary test result.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Urine acid/base parameters (titratable acid (TA), NH₄⁺, net acid excretion (NAE) and pH) were measured in bio-banked urine samples from controls (<i>n</i> = 10) and pwCF (<i>n</i> = 50) who completed the challenged urine HCO₃⁻ test. The association between urine acid/base excretion parameters and clinical CF disease characteristics and CFTR modulator therapy-induced changes were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Before treatment, challenged urine acid/base excretion associated with important CF disease characteristics. TA excretion and NAE were lower in pwCF with residual function mutations, 7.9 and 16.6 mmol/3 h, respectively, and lower TA excretion and NAE associated with pancreatic sufficiency. A lower excretion of TA, NH₄⁺, and NAE associated with a higher percentage of predicted FEV₁ (1.3%, 2.5% and 0.8% per mmol/3 h higher, respectively). Modulator treatment decreased TA excretion and NAE (−2.9 and −5.3 mmol/3 h, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Following acute NaHCO₃-loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO₃⁻ excretion sufficiently represents the additional urine acid/base parameters as test result. The observed changes in acid excretion support CFTR modulator-induced increase of CFTR-dependent type B intercalated cell HCO₃⁻ secretion and the use of the challenged urine HCO₃⁻ test as a possible CFTR-biomarker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteric glial NLRP3 inflammasome contributes to gut mucosal barrier alterations in a mouse model of diet‐induced obesity","authors":"Vanessa D'Antongiovanni, Matteo Fornai, Rocchina Colucci, Anna Nericcio, Laura Benvenuti, Clelia Di Salvo, Cristina Segnani, Clarissa Pierucci, Chiara Ippolito, Zoltan H. Nemeth, György Haskó, Nunzia Bernardini, Luca Antonioli, Carolina Pellegrini","doi":"10.1111/apha.14232","DOIUrl":"https://doi.org/10.1111/apha.14232","url":null,"abstract":"AimIn the present study, we investigated the involvement of NLRP3 inflammasome in the intestinal epithelial barrier (IEB) changes associated with obesity, and its role in the interplay between enteric glia and intestinal epithelial cells (IECs).MethodsWild‐type C57BL/6J and NLRP3‐KO (<jats:sup>−/−</jats:sup>) mice were fed with high‐fat diet (HFD) or standard diet for 8 weeks. Colonic IEB integrity and inflammasome activation were assessed. Immunolocalization of colonic mucosal GFAP‐ and NLRP3‐positive cells along with in vitro coculture experiments with enteric glial cells (EGCs) and IECs allowed to investigate the potential link between altered IEB, enteric gliosis, and NLRP3 activation.ResultsHFD mice showed increased body weight, altered IEB integrity, increased GFAP‐positive glial cells, and NLRP3 inflammasome hyperactivation. HFD‐NLRP3<jats:sup>−/−</jats:sup> mice showed a lower increase in body weight, an improvement in IEB integrity and an absence of enteric gliosis. Coculture experiments showed that palmitate and lipopolysaccharide contribute to IEB damage and promote enteric gliosis with consequent hyperactivation of enteric glial NLRP3/caspase‐1/IL‐1β signaling. Enteric glial‐derived IL‐1β release exacerbates the IEB alterations. Such an effect was abrogated upon incubation with anakinra (IL‐1β receptor antagonist) and with conditioned medium derived from silenced‐NLRP3 glial cells.ConclusionHFD intake elicits mucosal enteric gliotic processes characterized by a hyperactivation of NLRP3/caspase‐1/IL‐1β signaling pathway, that contributes to further exacerbate the disruption of intestinal mucosal barrier integrity. However, we cannot rule out the contribution of NLRP3 inflammasome activation from other cells, such as immune cells, in IEB alterations associated with obesity. Overall, our results suggest that enteric glial NLRP3 inflammasome might represent an interesting molecular target for the development of novel pharmacological approaches aimed at managing the enteric inflammation and intestinal mucosal dysfunctions associated with obesity.","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"32 1","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic intermittent hypoxia triggers cardiac fibrosis: Role of epididymal white adipose tissue senescent remodeling?","authors":"Suzain Naushad,&nbsp;Jonathan Gaucher,&nbsp;Zaineb Mezdari,&nbsp;Maximin Détrait,&nbsp;Elise Belaidi,&nbsp;Yanyan Zhang,&nbsp;Guillaume Vial,&nbsp;Sophie Bouyon,&nbsp;Gabor Czibik,&nbsp;Maria Pini,&nbsp;Sahar Aldekwer,&nbsp;Hao Liang,&nbsp;Véronique Pelloux,&nbsp;Judith Aron-Wisnewsky,&nbsp;Renaud Tamisier,&nbsp;Jean-Louis Pépin,&nbsp;Geneviève Derumeaux,&nbsp;Daigo Sawaki,&nbsp;Claire Arnaud","doi":"10.1111/apha.14231","DOIUrl":"10.1111/apha.14231","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Obstructive sleep apnea (OSA) is a growing health problem affecting nearly 1 billion people worldwide. The landmark feature of OSA is chronic intermittent hypoxia (CIH), accounting for multiple organ damage, including heart disease. CIH profoundly alters both visceral white adipose tissue (WAT) and heart structure and function, but little is known regarding inter-organ interaction in the context of CIH. We recently showed that visceral WAT senescence drives myocardial alterations in aged mice without CIH. Here, we aimed at investigating whether CIH induces a premature visceral WAT senescent phenotype, triggering subsequent cardiac remodeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a first experiment, 10-week-old C57bl6J male mice (<i>n</i> = 10/group) were exposed to 14 days of CIH (8 h daily, 5%–21% cyclic inspired oxygen fraction, 60 s per cycle). In a second series, mice were submitted to either epididymal WAT surgical lipectomy or sham surgery before CIH exposure. Finally, we used p53 deficient mice or Wild-type (WT) littermates, also exposed to the same CIH protocol. Epididymal WAT was assessed for fibrosis, DNA damages, oxidative stress, markers of senescence (p16, p21, and p53), and inflammation by RT-qPCR and histology, and myocardium was assessed for fibrosis and cardiomyocyte hypertrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CIH-induced epididymal WAT remodeling characterized by increased fibrosis, oxidative stress, DNA damage response, inflammation, and increased expression of senescent markers. CIH-induced epididymal WAT remodeling was associated with subtle and early myocardial interstitial fibrosis. Both epididymal WAT surgical lipectomy and p53 deletion prevented CIH-induced myocardial fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Short-term exposure to CIH induces epididymal WAT senescent remodeling and cardiac interstitial fibrosis, the latter being prevented by lipectomy. This finding strongly suggests visceral WAT senescence as a new target to mitigate OSA-related cardiac disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gender perspective on diet, microbiome, and sex hormone interplay in cardiovascular disease","authors":"Nina Jovanovic,&nbsp;Veronika Zach,&nbsp;Claudia Crocini,&nbsp;Lina Samira Bahr,&nbsp;Sofia Kirke Forslund-Startceva,&nbsp;Kristina Franz","doi":"10.1111/apha.14228","DOIUrl":"10.1111/apha.14228","url":null,"abstract":"<p>A unique interplay between body and environment embeds and reflects host–microbiome interactions that contribute to sex-differential disease susceptibility, symptomatology, and treatment outcomes. These differences derive from individual biological factors, such as sex hormone action, sex-divergent immune processes, X-linked gene dosage effects, and epigenetics, as well as from their interaction across the lifespan. The gut microbiome is increasingly recognized as a moderator of several body systems that are thus impacted by its function and composition. In humans, biological sex components further interact with gender-specific exposures such as dietary preferences, stressors, and life experiences to form a complex whole, requiring innovative methodologies to disentangle. Here, we summarize current knowledge of the interactions among sex hormones, gut microbiota, immune system, and vascular health and their relevance for sex-differential epidemiology of cardiovascular diseases. We outline clinical implications, identify knowledge gaps, and place emphasis on required future studies to address these gaps. In addition, we provide an overview of the caveats associated with conducting cardiovascular research that require consideration of sex/gender differences. While previous work has inspected several of these components separately, here we call attention to further translational utility of a combined perspective from cardiovascular translational research, gender medicine, and microbiome systems biology.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delaying post-exercise carbohydrate intake impairs next-day exercise capacity but not muscle glycogen or molecular responses","authors":"Javier Díaz-Lara,&nbsp;Elizabeth Reisman,&nbsp;Javier Botella,&nbsp;Bianka Probert,&nbsp;Louise M. Burke,&nbsp;David J. Bishop,&nbsp;Matthew J. Lee","doi":"10.1111/apha.14215","DOIUrl":"10.1111/apha.14215","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To investigate how delayed post-exercise carbohydrate intake affects muscle glycogen, metabolic- and mitochondrial-related molecular responses, and subsequent high-intensity interval exercise (HIIE) capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a double-blind cross-over design, nine recreationally active men performed HIIE (10 × 2-min cycling, ~94% W˙_peak) in the fed state, on two occasions. During 0–3 h post-HIIE, participants drank either carbohydrates (“Immediate Carbohydrate” [IC], providing 2.4 g/kg) or water (“Delayed Carbohydrate” [DC]); total carbohydrate intake over 24 h post-HIIE was matched (~7 g/kg/d). Skeletal muscle (sampled pre-HIIE, post-HIIE, +3 h, +8 h, +24 h) was analyzed for whole-muscle glycogen and mRNA content, plus signaling proteins in cytoplasmic- and nuclear-enriched fractions. After 24 h, participants repeated the HIIE protocol until failure, to test subsequent HIIE capacity; blood lactate, heart rate, and ratings of perceived effort (RPE) were measured throughout.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle glycogen concentrations, and relative changes, were similar between conditions throughout (<i>p</i> &gt; 0.05). Muscle glycogen was reduced from baseline (mean ± SD mmol/kg dm; IC: 409 ± 166; DC: 352 ± 76) at post-HIIE (IC: 253 ± 96; DC: 214 ± 82), +3 h (IC: 276 ± 62; DC: 269 ± 116) and + 8 h (IC: 321 ± 56; DC: 269 ± 116), returning to near-baseline by +24 h. Several genes (<i>PGC-1ɑ</i>, <i>p53</i>) and proteins (p-ACC^Ser79, p-P38 MAPK^{Thr180/Tyr182}) elicited typical exercise-induced changes irrespective of condition. Delaying carbohydrate intake reduced next-day HIIE capacity (5 ± 3 intervals) and increased RPE (~2 ratings), despite similar physiological responses between conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Molecular responses to HIIE (performed in the fed state) were not enhanced by delayed post-exercise carbohydrate intake. Our findings support immediate post-exercise refueling if the goal is to maximize next-day HIIE capacity and recovery time is ≤24 h.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal physical activity in healthy pregnancy: Effect on fetal oxygen supply","authors":"Mireille N. M. van Poppel,&nbsp;Annika Kruse,&nbsp;Anthony M. Carter","doi":"10.1111/apha.14229","DOIUrl":"10.1111/apha.14229","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We review evidence for effects of physical activity before and during gestation on the course of pregnancy and ask if there are circumstances where physical activity can stress the fetus due to competition for oxygen and energy substrates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first summarize physiological responses to exercise in nonpregnant people and known physiological adaptations to pregnancy. Comparing the two, we conclude that physical activity prior to and continuing during gestation is beneficial to pregnancy outcome. The effect of starting an exercise regimen during pregnancy is less easy to assess as few studies have been undertaken. Results from animal models suggest that the effects of maternal exercise on the fetus are transient; the fetus can readily compensate for a short-term reduction in oxygen supply.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In general, we conclude that physical activity before and during pregnancy is beneficial, and exercise started during pregnancy is unlikely to affect fetal development. We caution, however, that there are circumstances where this may not apply. They include the intensive exercise regimens of elite athletes and pregnancies at high altitudes where hypoxia occurs even in the resting state.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin modulates microbiota and improves blood pressure and cardiac remodeling in a rat model of hypertension","authors":"Moritz I. Wimmer,&nbsp;Hendrik Bartolomaeus,&nbsp;Harithaa Anandakumar,&nbsp;Chia-Yu Chen,&nbsp;Valentin Vecera,&nbsp;Sarah Kedziora,&nbsp;Sakshi Kamboj,&nbsp;Fabian Schumacher,&nbsp;Sidney Pals,&nbsp;Ariana Rauch,&nbsp;Jutta Meisel,&nbsp;Olena Potapenko,&nbsp;Alex Yarritu,&nbsp;Theda U. P. Bartolomaeus,&nbsp;Mariam Samaan,&nbsp;Arne Thiele,&nbsp;Lucas Stürzbecher,&nbsp;Sabrina Y. Geisberger,&nbsp;Burkhard Kleuser,&nbsp;Peter J. Oefner,&nbsp;Nadine Haase,&nbsp;Ulrike Löber,&nbsp;Wolfram Gronwald,&nbsp;Sofia K. Forslund-Startceva,&nbsp;Dominik N. Müller,&nbsp;Nicola Wilck","doi":"10.1111/apha.14226","DOIUrl":"10.1111/apha.14226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II-dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Metformin treatment increased the production of short-chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end-diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1-like gene expression in macrophages, reinforcing anti-inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 11","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142193842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}