Acta Physiologica最新文献

{"title":"Fatty Acid Taste Quality Information via GPR40 and CD36 in the Posterior Tongue of Mice","authors":"Yumiko Nagai,&nbsp;Kenichi Tokita,&nbsp;Keiko Yasumatsu","doi":"10.1111/apha.70071","DOIUrl":"https://doi.org/10.1111/apha.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Taste cells expressing GPR120 and connected chorda tympani nerve (CT) fibers are necessary for obtaining specific information on long-chain fatty acids (FA) in mice. However, the functions of GPR40, GPR120, and CD36 in the posterior part of the tongue remain unclear. Therefore, the present study has examined the neuron types coding for FA information in the glossopharyngeal (GL) nerve and their functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed single-fiber recordings in the GL nerve from GPR120-knockout (KO) and wild-type (WT) mice and behavioral preference tests based on five-minute intake using WT mice after the CT (and greater petrosal) nerves were sectioned bilaterally.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Single fibers were classified into FA-(F), S-, M-, electrolyte-(E), Q-type, and N-best groups, based on their maximal responses to oleic acid (OA), sucrose, monopotassium glutamate, HCl, quinine hydrochloride, and NaCl. Among the GL fibers, 3.8% of GPR120-KO and 11.8% of WT mice were F-type. Furthermore, 81.8% or more of the S- and M-type fibers showed responses to FAs in both mouse genotypes. Residual responses to FAs were substantially suppressed by GPR40 and CD36 antagonists in GPR120-KO mice. Preference scores for OA decreased significantly with the addition of CD36 or GPR40 antagonists. Additionally, the preference scores for monopotassium glutamate and sucrose decreased when the mice were conditioned to avoid OA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that GPR120 contributes only to the existence of F-type fibers and that CD36 and GPR40 mediate the palatable umami or sweet taste of FAs via the activation of S- and M-type fibers in the GL nerve.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273245","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":"Molecular Dynamics Simulations of a Putative Novel Mechanism for UCP1-Assisted FA Anion Transport","authors":"Sanja Vojvodić,&nbsp;Giorgia Roticiani,&nbsp;Mario Vazdar,&nbsp;Elena E. Pohl","doi":"10.1111/apha.70068","DOIUrl":"https://doi.org/10.1111/apha.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial energy can be stored as ATP or released as heat by uncoupling protein 1 (UCP1) during non-shivering thermogenesis in brown adipose tissue. UCP1, located in the inner mitochondrial membrane, reduces the proton gradient in the presence of long-chain fatty acids (FA). FA act as weak, protein-independent uncouplers, with the transport of the FA anion across the membrane being the rate-limiting step. According to the fatty acid cycling hypothesis, UCP1 catalyzes this step through an as-yet-undefined mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used computational and experimental techniques, including all-atom molecular dynamics (MD) simulations, membrane conductance measurements, and site-directed mutagenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified two novel pathways for fatty acid anion translocation (sliding) at the UCP1 protein–lipid interface, ending at key arginine residues R84 and R183 in a nucleotide-binding region. This region forms a stable complex with fatty acid anion, which is crucial for anion transport. Mutations of these two arginines reduced membrane conductance, consistent with the MD simulation prediction that the arachidonic acid anion slides between helices H2–H3 and H4–H5, terminating at R84 and R183. Protonation of the arachidonic acid anion predicts its release from the protein–lipid interface, allowing it to move to either cytosolic or matrix leaflets of the membrane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We provide a novel, detailed mechanism by which UCP1 facilitates fatty acid anion transport, as part of the fatty acid cycling process originally proposed by Skulachev. The residues involved in this transport are conserved in other SLC25 proteins, suggesting the mechanism may extend beyond UCP1 to other members of the superfamily.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256036","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":"Aquaporin-4-Mediated Water Permeability Rescues Aquaporin-3 Deficiency Caused Nephrogenic Diabetes Insipidus","authors":"Yi Ying,&nbsp;Zhiwei Qiu,&nbsp;Jihan Liu,&nbsp;Yazhu Quan,&nbsp;Yongpan An,&nbsp;Feng Lu,&nbsp;Keying Wang,&nbsp;Min Li,&nbsp;Hong Zhou,&nbsp;Baoxue Yang","doi":"10.1111/apha.70072","DOIUrl":"https://doi.org/10.1111/apha.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study was to determine whether water or solute transport plays a critical role in AQP3-mediated urine concentrating ability, using AQP3 knockout (AQP3-KO) mice and a novel mouse model in which the AQP3 gene coding region is replaced with AQP4 cDNA (AQP4-KI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>AQP3-KO and AQP4-KI mice were characterized using Western blot and immunofluorescence to confirm the absence of AQP3 and the in situ replacement of AQP4. Urinary output, osmolality and urea concentration were measured in mouse models under various conditions, including water deprivation, acute urea loading and high protein intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AQP3-KO mice exhibited a significantly increased daily urine output (6 times that in wild-type mice) and reduced urinary osmolality (&lt; 1000 mOsm/kg), with a marked inability to concentrate urea and osmolality in response to water deprivation, urea loading or high protein intake. In contrast, AQP4-KI mice showed restoration of urine output, urinary osmolality and urea concentration, approaching wild-type levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In situ replacement of AQP3 with AQP4 restores AQP3-mediated water permeability in the renal collecting duct, rescuing the nephrogenic diabetes insipidus (NDI) phenotype in AQP3-deficient mice. This study provides evidence that AQP3-mediated water permeability plays a crucial role in the renal urine concentrating mechanism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256035","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":"Multi-Wearable Approach for Monitoring Diurnal Light Exposure and Body Rhythms in Nightshift Workers","authors":"Steffen L. Hartmeyer,&nbsp;Nicholas E. Phillips,&nbsp;Friedrich C. Jassil,&nbsp;Céline Joris,&nbsp;Charna Dibner,&nbsp;Tinh-Hai Collet,&nbsp;Marilyne Andersen","doi":"10.1111/apha.70069","DOIUrl":"https://doi.org/10.1111/apha.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>As our understanding of light's impact on human health grows, studies examining light exposure and related health outcomes in everyday settings are increasingly important, particularly in high-risk groups like nightshift workers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this observational study, we monitored personal light exposure and physiological functions in a large cohort of healthcare nightshift workers using a spectrally resolved light dosimeter and wearable body temperature, actigraphy, and electrocardiography sensors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed a common occurrence of unfavorable light conditions during both shift types. During nightshift work, participants frequently experienced exposure to biologically potent cool-white LED lighting. On dayshifts, melanopic light levels often failed to meet recommended guidelines, with daylight as the primary source of bright light levels. Sleep duration, but not quality, significantly varied between shifts, with longer sleep before the first nightshift but shorter sleep on subsequent nights. Daytime and nighttime napping helped compensate for reduced sleep on nightshifts. Limited associations between light exposure and sleep were found, partially contradicting existing knowledge. Diurnal physiological and activity rhythms followed the change from day-active to night-active schedules; however, the change in physiological rhythms appeared partly dissociated from that of activity, suggesting a circadian modulation. Moreover, physiological functions exhibited bi-directional phase-shifts across consecutive nightshifts, which may have been mediated by differences in daytime light exposure before the first nightshift.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By employing a multi-wearable approach including recent sensors, we provide new insights into the lighting environments experienced by nightshift workers and the potential impact of nightshift work and light exposure on endogenous circadian rhythms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244487","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":"Revisiting Concepts of Thermal Physiology: Understanding Feedback and Feedforward Control, and Local Temperature Regulation","authors":"Duncan Mitchell,&nbsp;Shane K. Maloney,&nbsp;Edward P. Snelling,&nbsp;Robyn S. Hetem,&nbsp;Andrea Fuller","doi":"10.1111/apha.70063","DOIUrl":"https://doi.org/10.1111/apha.70063","url":null,"abstract":"<p>Most experts agree that the dominant mechanism through which body temperature is regulated, under a thermal challenge, environmental or metabolic, is negative feedback control. However, some consider negative feedback to be too sluggish to account for the rapid speed of response. The impression of sluggishness is based on an assumption that the body temperature that is regulated is a core temperature, whereas we concur with those who have concluded that what is regulated is an integrated temperature compiled from inputs from multiple body parts, including the skin. Negative feedback control is supplemented, though, by feedforward control, which is initiated by cues about the predicted magnitude and timing of the thermal challenge. Feedforward control is anticipatory because it can excite thermo-effectors in advance of the thermal challenge impacting on body temperature. Feedforward control is improved by learning but always is supervised by feedback control. There is disagreement about whether the pro-active excitation of thermo-effectors by temperature receptors in the skin occurs by fast feedback control or by feedforward control. We show that skin temperature receptors can provide physiologically meaningful negative feedback within seconds. Both the feedback and the feedforward regulation of integrated body temperature can be modulated by regulation of the temperature of body parts that have special thermoregulatory needs, notably the scrotum.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190664","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":"Branched-Chain Amino Acids and Di-Alanine Supplementation Attenuates Muscle Atrophy in a Murine Model of Cancer Cachexia","authors":"Mayra Colardo,&nbsp;Noemi Martella,&nbsp;Michela Varone,&nbsp;Daniele Pensabene,&nbsp;Giuseppina Caretti,&nbsp;Gianluca Bianchini,&nbsp;Andrea Aramini,&nbsp;Marco Segatto","doi":"10.1111/apha.70067","DOIUrl":"https://doi.org/10.1111/apha.70067","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cancer cachexia is a severe metabolic disorder leading to skeletal muscle atrophy. Muscle wasting is a major clinical problem in cachectic patients, as it limits the efficacy of chemotherapeutic treatments and worsens quality of life. Nutritional support based on branched-chain amino acids (BCAA) has been shown to be a promising approach to counteract cachexia-induced muscle atrophy, but its efficacy is still debated. Furthermore, the putative role of di-alanine (Di-Ala) supplementation has yet to be evaluated. The present study therefore sought to assess whether BCAA supplementation, alone or in combination with a Di-Ala peptide, could attenuate muscle wasting in a preclinical model of cancer cachexia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To this end, C26 tumor-bearing mice were administered BCAA supplementation, with or without Di-Ala. Body and muscle weights, as well as molecular, biochemical, and morphological analysis, were carried out to characterize prospective changes of markers involved in cachexia and muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The main findings revealed that BCAA supplementation effectively prevented body weight loss and muscle atrophy. Of note, Di-Ala significantly amplified the effects of BCAA. These phenomena were found to be mediated by the suppression of pathways involved in protein catabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, these results highlight that innovative formulations containing Di-Ala, capable of increasing BCAA bioavailability, may be efficacious in counteracting muscle atrophy, especially during mild-to-moderate cancer cachexia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179218","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":"Lack of Synaptic Adhesion Proteins Makes Zebrafish More Anxious and Less Aggressive","authors":"Maja R. Adel,&nbsp;Florian Freudenberg","doi":"10.1111/apha.70065","DOIUrl":"https://doi.org/10.1111/apha.70065","url":null,"abstract":"&lt;p&gt;In this issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Tatzl et al. [&lt;span&gt;1&lt;/span&gt;] investigate the relevance of the &lt;i&gt;leucine-rich repeat transmembrane protein 4 like 1&lt;/i&gt; (&lt;i&gt;lrrtm4l1&lt;/i&gt;) gene, a zebrafish orthologue of the human &lt;i&gt;LRRTM4&lt;/i&gt;, on behavioral, transcriptomic, and metabolomic readouts in mixed sex adult zebrafish (summarized in Figure 1). &lt;i&gt;LRRTM4&lt;/i&gt; is one of four members of the &lt;i&gt;LRRTM&lt;/i&gt; gene family, which code for synaptic cell adhesion molecules that promote excitatory synapse development, including synaptic insertion and stabilization of AMPA receptors. &lt;i&gt;LRRTM4&lt;/i&gt; is associated with neurodevelopmental disorders, including autism spectrum disorder (ASD) and attempted suicide [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Using RNASeq, the authors identified 126 differentially expressed genes in the telencephalon of &lt;i&gt;lrrtm4l1&lt;/i&gt; knockout (&lt;i&gt;lrrtm4l1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt;) fish. Among these, they highlight the upregulation of &lt;i&gt;rimkla&lt;/i&gt; and &lt;i&gt;arhgap12&lt;/i&gt;. The &lt;i&gt;rimkla&lt;/i&gt; gene is linked to cognition and memory consolidation [&lt;span&gt;3&lt;/span&gt;]. The mammalian orthologue of the &lt;i&gt;arhgap12b&lt;/i&gt; gene (i.e., &lt;i&gt;ARHGAP12&lt;/i&gt;) promotes endocytosis of postsynaptic AMPA receptors, opposing the effect of &lt;i&gt;LRRTM4&lt;/i&gt; [&lt;span&gt;4&lt;/span&gt;]. Notable downregulated genes include &lt;i&gt;tyrosine hydroxylase&lt;/i&gt;, essential for catecholamine synthesis, and &lt;i&gt;plasmolipin&lt;/i&gt;, encoding a major component of myelin sheaths; both genes have previously been linked to various disorders. Pathway analyses implicated semaphorin-plexin signaling, as well as fatty acid metabolism and degradation, as well as valine, leucine, and isoleucine degradation. Semaphorin-plexin signaling is involved in axon guidance and neuronal morphogenesis during neurodevelopment and might stabilize synaptic transmission both during development and adulthood [&lt;span&gt;5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Consistent with the differentially expressed genes, metabolomic changes in &lt;i&gt;lrrtm4l1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; zebrafish revealed elevated levels of homovanillic acid, the end product of dopamine metabolism, and lower levels of adenosine. Additionally, &lt;i&gt;lrrtm4l1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; zebrafish showed a trend toward higher serotonin and lower melatonin levels. Unbiased metabolite feature analysis revealed six significant features, including two upregulated features with fragmentation profiles similar to phospholipids and one downregulated feature that was similar to methyl vanillate.&lt;/p&gt;&lt;p&gt;To investigate the consequences of the observed transcriptomic and metabolic alterations, the authors performed several behavioral experiments in &lt;i&gt;lrrtm4l1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; and wild-type zebrafish. In the open field test, &lt;i&gt;lrrtm4l1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;−/−&lt;/i&gt;&lt;/sup&gt; fish displayed a lower total distance traveled and nominally increased immobile time. Additionally, their swimming movements appeared more erratic, and they displayed increased thigmotaxis, a potential indicator of increased anxiety-like behavior. The increased a","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171862","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":"Secretagogin, Driven by Neuronal Activity, Transiently Regulates Exocytosis During Development","authors":"Robert Zorec,&nbsp;Alexei Verkhratsky","doi":"10.1111/apha.70066","DOIUrl":"https://doi.org/10.1111/apha.70066","url":null,"abstract":"&lt;p&gt;Fluctuations of intracellular ionic concentrations are powerful signaling tools in living cells [&lt;span&gt;1&lt;/span&gt;]. Among these ions, Ca&lt;sup&gt;2+&lt;/sup&gt; plays a well-documented and ubiquitous role in the regulation of cellular events, ranging from development and growth to intercellular signaling and information processing, and, ultimately, Ca&lt;sup&gt;2+&lt;/sup&gt; regulates cell survival or cell death. All these effects are mediated through the extended family of Ca&lt;sup&gt;2+&lt;/sup&gt;-sensors.&lt;/p&gt;&lt;p&gt;A recent paper published by Alpar, Harkany, and their coworkers in Acta Physiologica [&lt;span&gt;2&lt;/span&gt;] revealed a complex and developmentally regulated signaling network centered on dynamic changes of expression of the archetypal Ca&lt;sup&gt;2+&lt;/sup&gt; sensor, secretagogin. They show that changes in secretagogin expression are affected by neuronal activity, and therefore establish a novel link between excitation and intracellular signaling processing. The study of Hanics et al. critically challenges the notion of secretagogin, used widely as a neuronal marker, as a static marker by demonstrating its dynamic expression in response to neuronal activity during mammalian brain development. Using a combination of human foetal brain mapping, genetically modified mice (Scgn-iCre::Ai9), single-cell RNA sequencing, and both in vitro and in vivo activity manipulation models, the authors provide compelling evidence that secretagogin expression is both developmentally regulated and sensitive to neuronal activity.&lt;/p&gt;&lt;p&gt;One of the main functions of Ca&lt;sup&gt;2+&lt;/sup&gt; sensors in the information processing loops of the central nervous system is the regulation of vesicular neurotransmitter release. Fusion of the vesicle membrane with the plasma membrane, known as exocytosis, leads to the formation of a water-filled channel, the fusion pore, a conduit for molecules in the vesicle lumen to exit into the extracellular space. This evolutionary invention emerged in primordial eukaryotic cells [&lt;span&gt;3-5&lt;/span&gt;] and mediates a myriad of processes, including the release of neurotransmitters, hormones, and other signaling molecules, all essential for maintaining cell-to-cell communication in multicellular organisms. The release of vesicle content may occur only if the fusion pore widens sufficiently. Over seven decades ago, Bernard Katz proposed that the fusion pore opens completely upon exocytosis. Therefore, since those days, the fusion mechanism has been intensively studied, mainly focusing on how the merger of the two membranes occurs. This led to the discovery of SNARE proteins, targets of proteolytic botulinum neurotoxins, and the concept that a rather complex array of events, including vesicle priming and docking at the active zone to fusion pore formation upon an increase in cytosolic Ca&lt;sup&gt;2+&lt;/sup&gt;, mediates stimulus-secretion coupling to within milliseconds [&lt;span&gt;6&lt;/span&gt;]. Secretagogin is linked to regulated exocytosis through an extended interactome which includes SNAP-23, DOC2α, ARFGAP2","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171973","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":"Specialized Pro-Resolving Mediators as Emerging Players in Cardioprotection: From Inflammation Resolution to Therapeutic Potential","authors":"Anna De Bartolo,&nbsp;Naomi Romeo,&nbsp;Tommaso Angelone,&nbsp;Carmine Rocca","doi":"10.1111/apha.70062","DOIUrl":"https://doi.org/10.1111/apha.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Timely myocardial reperfusion is essential for restoring blood flow to post-ischemic tissue, thereby reducing cardiac injury and limiting infarct size. However, this process can paradoxically result in additional, irreversible myocardial damage, known as myocardial ischemia–reperfusion injury (MIRI). The goal of this review is to explore the role of specialized pro-resolving mediators (SPMs) in atherosclerosis and MIRI, and to assess the therapeutic potential of targeting inflammation resolution in these cardiovascular conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review summarizes current preclinical and clinical evidence on the involvement of SPMs in the pathogenesis of atherosclerosis and MIRI, acknowledging that several cellular and molecular aspects of their mechanisms of action remain to be fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MIRI is a complex phenomenon in which inflammation, initially triggered during ischemia and further amplified upon reperfusion, plays a central role in its pathogenesis. Various cellular and molecular players mediate the initial pro-inflammatory response and the subsequent anti-inflammatory reparative phase following acute myocardial infarction (AMI), contributing both to ischemia- and reperfusion-induced damage as well as to the healing process. SPMs have emerged as key endogenous immunoresolvents with potent anti-inflammatory, antioxidant, and pro-resolving properties that contribute to limit excessive acute inflammation and promote tissue repair. While dysregulated SPM-related signaling has been linked to various cardiovascular diseases (CVD), their precise role in AMI and MIRI remains incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Targeting inflammation resolution may represent a promising therapeutic strategy for mitigating atheroprogression and addressing a complex condition such as MIRI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148311","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":"Lactate Refurbished: Cardiovascular Support During Metabolic Stress and Fuel Rather Than Waste","authors":"Cor de Wit","doi":"10.1111/apha.70064","DOIUrl":"https://doi.org/10.1111/apha.70064","url":null,"abstract":"&lt;p&gt;For decades, lactate was considered a metabolic waste product that is produced and released from cells during (relative) lack of oxygen. In the glycolytic pathway, glucose is metabolized to pyruvate that fuels the Krebs cycle in mitochondria where oxygen is required for complete pyruvate oxidation. It was thought that pyruvate accumulates during oxygen lack and is subsequently reduced to lactate with concomitant NADH consumption and regeneration of NAD&lt;sup&gt;+&lt;/sup&gt;. The equilibrium of the reaction is determined by the lactate/pyruvate ratio and the cytosolic redox potential (NADH/NAD&lt;sup&gt;+&lt;/sup&gt; ratio) leading to 10-fold higher concentrations of lactate than pyruvate in resting skeletal muscle. This generated the idea that lactate is the final product of the glycolytic pathway and, in fact, links glycolysis to oxidative metabolism [&lt;span&gt;1&lt;/span&gt;]. Interestingly, lactate is also produced under aerobic conditions, that is at pO&lt;sub&gt;2&lt;/sub&gt; values well above the critical mitochondrial pO&lt;sub&gt;2&lt;/sub&gt;. Lactate production is even enhanced in exercising skeletal muscle because glycolysis is stimulated more intensely than oxidative phosphorylation [&lt;span&gt;2&lt;/span&gt;]. Therefore, lactate is also released into the bloodstream from working muscle providing a dynamic fuel source that may be taken up and metabolized by other organs including brain and heart, which are known to eagerly combust lactate from blood [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;This concept turns the spotlight on lactate as an important player in metabolism during exercise. It may not only be shuttled from the cytosol to mitochondria but also from cell to cell and tissue to tissue via the bloodstream [&lt;span&gt;1&lt;/span&gt;] providing a valuable energy source for tissues that do not exhibit large energy stores. In this context, the work of Homilius and colleagues published in this issue [&lt;span&gt;4&lt;/span&gt;] provides interesting new insight by characterizing the impact of lactate on cardiovascular homeostasis. They demonstrate that adjustments required in the cardiovascular system with enhanced cellular metabolism during exercise are uniquely induced by this valuable metabolite (Figure 1).&lt;/p&gt;&lt;p&gt;Homilius and colleagues [&lt;span&gt;4&lt;/span&gt;] studied the vascular effects of different conjugate bases that are produced during cellular metabolism or by the microbiome. Effects of protons were eliminated by keeping pH constant. Precontracted arteries isolated from different vascular beds from rats relaxed largely or even fully in response to bases of possible microbial origin (acetate, propionate, butyrate) at seemingly high concentrations (10 mmol/L). Endogenously produced bases were less efficacious (lactate, hydroxybutyrate), but still achieved considerable relaxations of 25%–50% in different arteries, with pronounced relaxations in femoral and coronary arteries, after 5 min at concentrations found during exercise (EC50: ~10 mmol/L). Other bases were without substantial effect (pyruvate, malonate, succinate). In marked cont","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 7","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148593","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}