Acta Physiologica最新文献

{"title":"Myophosphorylase Knock Out Prevents the Exaggerated Exercise Pressor Reflex in Rats With Simulated Peripheral Artery Disease","authors":"Guillaume P. Ducrocq,&nbsp;Laura Anselmi,&nbsp;Victor Ruiz-Velasco,&nbsp;Marc P. Kaufman","doi":"10.1111/apha.70172","DOIUrl":"10.1111/apha.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Controversy exists on which metabolites determine the exaggerated exercise pressor reflex (EPR) in peripheral artery disease (PAD). In decerebrated rats, we investigated the role played by lactate and hydrogen ions in a model of PAD, which was simulated by ligating the femoral artery for 72 h before the start of the experiment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Production of lactate and hydrogen ions by the contracting hindlimb muscles was manipulated by knocking out the myophosphorylase gene (pygm). In both knockout (pygm^−/−; <i>n</i> = 13; 6-females) and wild-type rats (pygm^+/+; <i>n</i> = 14; 7-females), the EPR was evoked by statically contracting the triceps-surae muscles. Blood pressure, tension, and renal sympathetic nerve activity were measured. Responsiveness of the metabolic component of the EPR was evaluated by intra-arterial injections of lactic acid and diprotonated phosphate solutions. Responsiveness of the mechanical component of the EPR was evaluated by stretching the calcaneal tendon. In each rat, the pressor responses evoked from the freely perfused triceps-surae muscles were compared to those evoked from the contralateral ischemic triceps-surae muscles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In pygm^+/+ rats whose femoral artery was ligated, static contraction, lactic-acid injection and diprotonated phosphate injection evoked pressor responses that were 88%, 22%, and 58% greater than those evoked from muscles whose femoral arteries were freely perfused. In pygm^−/− rats, ligation of the femoral artery for 72 h had no effect. In both groups, 72 h of femoral artery ligation exacerbated the pressor response to passive stretch.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lactate and hydrogen-ions accumulation in contracting myocytes plays a key role in exaggerating the metabolic component of the EPR evoked from hindlimb muscles with chronically-ligated femoral arteries.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199720","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":"Alms1 KO Rat: A New Model of Cardiometabolic Syndrome With Spontaneous Hypertension","authors":"Ankita B. Jaykumar,&nbsp;Sumit R. Monu,&nbsp;Jiang Xu,&nbsp;Mariela Mendez,&nbsp;Xiao-Ping Yang,&nbsp;Nour-Eddine Rhaleb,&nbsp;Pablo A. Ortiz","doi":"10.1111/apha.70174","DOIUrl":"10.1111/apha.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Alström syndrome 1 (ALMS1) is a protein linked to Alström syndrome, a rare genetic disorder characterized by obesity, insulin resistance, hyperinsulinemia, and hypertension. Genetic studies have further associated <i>Alms1</i> with hypertension in human populations. However, the precise mechanisms by which ALMS1 regulates metabolic and cardiovascular function remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this study, we investigate metabolic and cardiovascular functions regulated by ALMS1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate this, we developed and characterized an <i>Alms1</i> knockout (KO) rat model, which spontaneously develops metabolic syndrome and hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings reveal that <i>Alms1</i> KO rats exhibit age-dependent metabolic dysfunction, with hypertension and increased body weight becoming evident by 10–12 weeks of age. Obesity, hyperinsulinemia, and vascular dysfunction emerge later, at 14–16 weeks, suggesting progressive metabolic deterioration. Notably, <i>Alms1</i> KO rats develop hyperleptinemia as early as 7 weeks, prior to the onset of obesity, implicating ALMS1 in early leptin regulation and metabolic signaling. Moreover, female <i>Alms1</i> KO rats develop severe metabolic syndrome with hypertension, like males, demonstrating a lack of the typical female cardiovascular protection. Echocardiographic analysis shows progressive cardiac dysfunction, including left ventricular (LV) dilation, increased wall thickness, and impaired contractility. Despite these structural changes, the LV mass/BW ratio remains unchanged, suggesting a shift toward maladaptive eccentric remodeling rather than hypertrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, these findings establish the <i>Alms1</i> KO rat as a robust preclinical model of metabolic syndrome. This model closely mimics human disease and provides a powerful tool for studying the mechanisms of metabolic and cardiovascular dysfunction as well as for testing potential therapeutic interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197059","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":"Cell Type-Specific Loss of SIRT1 in Central Amygdala Leads to Depression-Like Behaviors by Altering Neuronal Excitability in Mice","authors":"Hui Huang,&nbsp;Xiao-Bao Ding,&nbsp;Yu-Wen Lin,&nbsp;Wen-Li Hu,&nbsp;Chen-Rui Zhou,&nbsp;Tian-Qi Chen,&nbsp;Yue Zhou,&nbsp;Wei Dong,&nbsp;Cheng-Hua Zhou,&nbsp;Yu-Qing Wu","doi":"10.1111/apha.70176","DOIUrl":"10.1111/apha.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The current understanding of the underlying pathogenesis of depression is still limited. Silent information regulator 1 (SIRT1) has been shown to mediate the development of depression. However, the underlying mechanisms are not well understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SIRT1^flox/flox mice were used to observe the effect of selective knockdown of SIRT1 in glutamatergic or GABAergic neurons of the central amygdala (CeA) on depression-like behaviors. Western blot and immunofluorescence staining were used to determine the protein levels. Optogenetic technology was used to manipulate neuronal excitability. Whole cell patch-clamp recordings and c-Fos immunofluorescence staining were used to detect the excitability of different types of neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study demonstrated that selective knockdown of SIRT1 in CeA glutamatergic neurons induced depression-like behaviors and increased the excitability of glutamatergic neurons in mice. Optogenetic inhibition of glutamatergic neurons in CeA significantly ameliorated the depression-like behaviors induced by downregulation of SIRT1 in CeA glutamatergic neurons. In addition, selective knockdown of SIRT1 in CeA GABAergic neurons could also induce depression-like behaviors, accompanied by decreased excitability of GABAergic neurons and increased excitability of glutamatergic neurons. Optogenetic activation of GABAergic neurons in CeA significantly alleviated the depression-like behaviors induced by downregulation of SIRT1 in CeA GABAergic neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that cell-type-specific loss of SIRT1 may mediate the development of depression-like behaviors in mice by divergent changes in the excitability of CeA glutamatergic and GABAergic neurons. These data demonstrate a new mechanism for the development of depression and provide a potential therapeutic target for depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163126","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":"An Overlooked Form of Non-Shivering Thermogenesis in Skeletal Muscle","authors":"Shane K. Maloney,&nbsp;Duncan Mitchell","doi":"10.1111/apha.70175","DOIUrl":"10.1111/apha.70175","url":null,"abstract":"&lt;p&gt;The taxonomic class of mammals is characterized by its ability to produce milk, but several other features distinguish mammals from their reptile ancestors. A debated hallmark that has attracted much attention, shared with birds, is endothermic homeothermy—the capacity to maintain a high and stable body temperature independent of environmental heat sources—which reptiles generally cannot do.&lt;/p&gt;&lt;p&gt;Endothermy is an expensive undertaking that requires the ability to increase and control the rate of metabolic heat generation [&lt;span&gt;1&lt;/span&gt;]. To retain the metabolic heat, mammals also evolved external insulation, notably in the form of fur, and did so before they evolved the ability to give birth to live young, as evidenced by the endothermic monotreme mammals having fur but being egg layers. Reproduction might have been a factor in the evolution of endothermy because some python species [&lt;span&gt;2&lt;/span&gt;] and the tegu [&lt;span&gt;3&lt;/span&gt;] have some capacity for endothermy, but only in their reproductive phases.&lt;/p&gt;&lt;p&gt;In unstressed inactive mammals most metabolic heat is the waste heat generated by cellular biochemical processes, the energetics of which is measured as the basal metabolic rate (BMR). BMR of mammals generally is about 10 times that of reptiles. No specific organ or tissue is responsible for that “constitutive” heat production. Ion pumps are ubiquitous and intrinsically inefficient, and their activity releases waste heat in all cells. Leakier membranes in mammalian than in reptile cells, leading to a requirement for elevated activity of ion pumps, can explain much of the elevated BMR of mammals over reptiles [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;When a mammal is exposed to cold, the rate that heat is lost from the body to the environment can be alleviated by peripheral vasoconstriction. Many reptiles also seem to adjust their rate of environmental heat gain/loss by adjusting peripheral perfusion [&lt;span&gt;1&lt;/span&gt;]. If vasoconstriction fails to arrest the fall in body temperature, mammals increase metabolic heat production to match the rate of heat loss [&lt;span&gt;5, 6&lt;/span&gt;]. The “extra” thermogenesis adds to the cost of living, but presumably those costs are outweighed by the advantages of defending the high and stable body temperature. Whether endothermic homeothermy evolved via a selection pressure for the advantages of high and stable body temperature, or a selection pressure that favored some other facet of biology that ended up being correlated to a high body temperature, such as aerobic capacity [&lt;span&gt;1&lt;/span&gt;], is still debated. More is known about the mechanisms of thermogenesis, in the form of shivering and non-shivering thermogenesis.&lt;/p&gt;&lt;p&gt;Shivering thermogenesis does not occur in reptiles but is well characterized in humans and other mammals. Shivering involves rhythmic, involuntary, uncoordinated contraction of skeletal muscle fascicles that are made up of individual muscle cells (myocytes) [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The first type of non-shiver","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155537","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":"Heterogenous Calcium Response in Arterial and Venous Endothelial Cells","authors":"Yu-xiang Wang,&nbsp;Qi Chen","doi":"10.1111/apha.70169","DOIUrl":"10.1111/apha.70169","url":null,"abstract":"&lt;p&gt;Calcium signaling plays a central regulatory role in different types of cells [&lt;span&gt;1&lt;/span&gt;]. In a recent issue of Acta Physiologica, Lee and colleagues report that endothelial cells within both arteries and veins display a surprising high degree of heterogeneity and differences in their calcium responses to agonists [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Vascular endothelial cells (VECs) are one of the most fundamental cell types in vertebrates, lining the most inner side of our blood vessels [&lt;span&gt;3&lt;/span&gt;]. In VECs, calcium signaling acts as a key mediator for transducing extracellular cues to induce multiple intracellular signal responses and is essential to direct sprouting angiogenesis, modulate inflammatory responses, and to maintain vascular homeostasis. Numerous previous studies have revealed the complexity and functional diversity of calcium signaling in VECs, offering insights to understand the response of VECs during physiological and pathological conditions [&lt;span&gt;4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;During vascular development and sprouting angiogenesis, calcium signaling plays an instructive role in endothelial cell behavior. Studies using zebrafish models have demonstrated that Piezo1-mediated mechanosensitive calcium activity is crucial for endothelial tip cell navigation. High-frequency calcium transients promote branch retraction through calpain activation, whereas low-frequency transients stimulate branch extension via nitric oxide synthase. This frequency-dependent calcium signaling determines the proper formation of vascular networks. In piezo1 mutants, reduced calcium activity leads to unbalanced branching and disorganized vascular structures, underscoring the integrative role of mechano-chemical mediated calcium signaling during angiogenesis [&lt;span&gt;6&lt;/span&gt;]. Similarly, the calcium-permeable channel TRPC1 has been shown to mediate vascular endothelial cell growth factor A induced angiogenesis. Loss of TRPC1 impairs intersegmental vessel sprouting and growth, disrupting filopodia extension, cell migration, and division. These effects are endothelial cell–autonomous and depend on activation of the ERK signaling pathway [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Calcium signaling also exhibits precise spatiotemporal control in the regulation of vascular barrier function and inflammation. Under steady state conditions, endothelial cells maintain low intracellular calcium levels through pumps such as PMCA and SERCA, which preserve barrier integrity. Upon inflammatory stimulation, mediators including thrombin and histamine activate the GPCR–PLC–IP₃ pathway, leading to calcium release and activation of downstream effectors such as CaM/CaMKII. This cascade triggers VE-cadherin disassembly and cytoskeletal remodeling, thereby increasing vascular permeability [&lt;span&gt;8&lt;/span&gt;]. During leukocyte transendothelial migration, however, calcium signaling is spatially confined rather than global. The PECAM1 interactions activate TRPC6 channels, inducing localized calcium influx that p","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140285","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-Mediated Mechanotransduction: Orchestrating the Dynamic Response of Podocytes and Parietal Epithelial Cells to Mechanical Stress","authors":"Maria Elena Melica,&nbsp;Giulia Antonelli,&nbsp;Anna Julie Peired,&nbsp;Laura Lasagni","doi":"10.1111/apha.70173","DOIUrl":"10.1111/apha.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The glomerulus is a specialized microvascular unit that filters plasma through the coordinated function of podocytes and parietal epithelial cells (PECs). From this perspective, the glomerulus functions like a living hydrogeological filtration system. This review aims to integrate mechanobiology and hydrogeology, reframing podocytes and PECs as active regulators in a pressure-driven network, with Piezo1 central to glomerular homeostasis, adaptation, and pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review integrates existing literature on glomerular biology, mechanosensitive signaling, and epithelial cell function, focusing on podocytes, PECs, and mechanosensitive structures such as the Piezo1 channel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Podocytes form interdigitating foot processes connected by the slit diaphragm, forming both a selective barrier against protein loss and a mechanosensory interface. Through mechanosensitive structures, such as the Piezo1 channel, podocytes detect variations in hydrostatic pressure and transduce these cues into intracellular signaling that regulates permeability and preserves structural integrity. Sustained mechanical stress, however, can compromise podocyte function and viability. PECs line Bowman capsule, forming an impermeable boundary surrounding the filtration core. Once considered passive, PECs exhibit dynamic properties: some retain progenitor-like potential, contributing to repair, whereas others promote fibrosis in disease conditions. In this analogy, blood flow replaces groundwater while the multilayered filtration barrier mirrors stratified geological formations. Podocytes function as biological piezometers—sensing pressure and modulating filtration—while PECs resemble aquicludes, defining impermeable boundaries that can constrain or reshape the system under mechanical or inflammatory challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>By integrating mechanobiology and hydrogeology, this review reframes the glomerulus as a living, pressure-driven filtration system in which podocytes and PECs act as active regulators rather than passive structural elements, with Piezo1 playing a central role in glomerular homeostasis, adaptation, and pathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12883315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140334","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":"Ketone Monoester Increases Skeletal Muscle Power and Energy Turnover in Older but Not Young Men Without Affecting Metabolic Economy: A Controlled, Double Blind, Cross-Over Trial","authors":"Ole Emil Andersen,&nbsp;Ryan Godsk Larsen,&nbsp;Niels Møller,&nbsp;Anders Stouge,&nbsp;Steffen Ringgaard,&nbsp;Kristian Overgaard,&nbsp;Niels Jessen","doi":"10.1111/apha.70161","DOIUrl":"10.1111/apha.70161","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Ketosis may represent a therapeutic target for age-related impairments in skeletal muscle function. This study investigated acute effects of ketosis on metabolic economy, mitochondrial function, and contractile parameters in skeletal muscle of young and older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twelve young (20–25 years) and twelve older (65–85 years) healthy men, matched by age-adjusted V̇O₂max, participated in a randomized, crossover, double-blind intervention with ingestion of ketone monoester or placebo on separate study days. On both days, a low-dose, continuous glucose infusion blocked endogenous ketone production. Metabolic economy, oxidative capacity, muscle performance, intramuscular pH, and relative decline in peak power were assessed in the tibialis anterior through phosphorous MR spectroscopy (³¹P-MRS) and dynamometer recordings. Mitochondrial function of the quadriceps femoris muscle was assessed by high-resolution respirometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ketosis had no effect on metabolic economy in either young or older participants. The older group showed lower metabolic economy compared to the young group. In older participants, ketones increased ATP production and time-torque derived work capacity. Oxidative capacity was similar between groups and remained unaffected by ketones. In the older group, ketones improved peak power and increased both muscle relative decline in peak power and contraction-induced pH decline. Complex I + II respiration was lower in older compared to young participants, with no effect of ketones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ketosis enhanced skeletal muscle work capacity and ATP production in older but not young adults, suggesting an age-specific effect of ketone bodies on muscle function that operates independently of changes in metabolic economy and mitochondrial function. These findings support ketosis as a promising ergogenic therapy for older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The study was pre-registered at clinicaltrials.gov (NCT05732909)</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123054","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":"WDR72 Is Required for Urinary Acidification and Normal H+-ATPase Activity in Intercalated Cells in Mice","authors":"Hannah Auwerx,&nbsp;Moana Busch-Dohr,&nbsp;Xiaoxu Li,&nbsp;Carsten A. Wagner,&nbsp;Soline Bourgeois","doi":"10.1111/apha.70165","DOIUrl":"10.1111/apha.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Biallelic inactivating <i>WDR72</i> variants are linked to distal renal tubular acidosis (dRTA), nephrocalcinosis, and amelogenesis imperfecta. The kidney shows high <i>WDR72</i> expression; its precise localization and function remain unclear. WDR72 is a member of the WD40 repeat domain protein family—a large group of scaffold proteins involved in various pathways, including vesicular trafficking—which has been suggested as a potential role for WDR72. This study investigates WDR72 expression and its role in renal acid–base homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed <i>WDR72/Wdr72</i> expression in single-cell transcriptome data from human and murine kidneys. We characterized <i>Wdr72</i>^{<i>−/−</i>} female and male mice and assessed <i>Wdr72</i> mRNA and protein localization, the ability of the kidney to excrete acid, and the expression and function of the H⁺-ATPase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transcriptome data showed that <i>WDR72/Wdr72</i> is highly expressed in intercalated cells and other nephron segments. Immunohistochemistry localized WDR72 mostly at the apical membrane of type A-intercalated cells (A-IC). <i>Wdr72</i>^{<i>−/−</i>} mice exhibited alkaline urine under normal conditions, but only female knockout mice developed a pronounced metabolic acidosis upon dietary acid loading. Western blot analyses revealed sex-dependent WDR72 expression changes with acid loading. Expression of several H⁺-ATPase subunits was dysregulated in <i>Wdr72</i>^{<i>−/−</i>} kidneys while their localization in intercalated cells remained intact. Lower expression of H⁺-ATPase subunits was paralleled by reduced H⁺-ATPase activity observed in isolated microperfused collecting ducts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings identify WDR72 as a critical regulator of type A-intercalated cell dependent urinary acidification, modulating H⁺-ATPase activity. The sex-specific metabolic phenotype reveals a novel mechanism underlying sex differences in renal acid handling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12869471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111491","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":"Glucagon-Like Peptide-1 Receptor Agonists in Obesity-Induced Respiratory Pathophysiology","authors":"Melanie Alexis Ruiz,&nbsp;Thales Henrique do Carmo Furquim,&nbsp;Dashdulam Davaanyam,&nbsp;Noah R. Williams,&nbsp;Vsevolod Y. Polotsky,&nbsp;Mateus R. Amorim","doi":"10.1111/apha.70171","DOIUrl":"10.1111/apha.70171","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111451","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":"ClC-2 Contributes to Hypotonicity-Induced Adrenal Aldosterone Secretion","authors":"Marina Volkert,&nbsp;Hoang An Dinh,&nbsp;Ute I. Scholl,&nbsp;Gabriel Stölting","doi":"10.1111/apha.70168","DOIUrl":"10.1111/apha.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The zona glomerulosa (ZG) of the adrenal cortex regulates blood pressure and electrolyte homeostasis through aldosterone production. In ZG cells, potassium and angiotensin II (Ang II) trigger calcium oscillations that drive aldosterone synthesis. Changes in serum osmolality also modulate aldosterone production in a chloride-dependent fashion, but the involved proteins remain unclear. Because the chloride channel ClC-2 is activated by hypoosmolality, we investigated its role in ZG osmoregulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used <i>Clcn2</i> knockout (KO) and wild-type (WT) mice. Explanted adrenal glands were incubated with iso- and hypotonic solutions for measurements of aldosterone. Acute adrenal slices were studied using calcium and chloride sensitive fluorescent dyes. We also investigated ClC-2's systemic importance by inducing a hyponatremic hypoosmolality in mice using desmopressin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Under hypoosmolar conditions, WT adrenals upregulated aldosterone production in vitro, an effect that was absent in the KO. WT cells responded to hypoosmolality with increased intracellular calcium levels. This response was abrogated in KO cells. Intracellular chloride levels were higher in ZG cells from KO adrenal slices. This suggests that ClC-2 provides a hypoosmolality-dependent chloride efflux pathway that is missing in the KO. Systemic hypoosmolality in mice induced by desmopressin did not differentially affect blood aldosterone levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ClC-2 plays a role in the ZG's response to reduced extracellular osmolality through chloride outflow, which likely causes depolarization, voltage-dependent calcium influx, and aldosterone production. These data advance our understanding of regulators of aldosterone production.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 3","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12852535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091574","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}