Acta Physiologica最新文献

{"title":"Not a Messenger, but Lots to Say: New Insights on Long Noncoding RNAs in the Kidney","authors":"Alexandria Juffre","doi":"10.1111/apha.70305","DOIUrl":"10.1111/apha.70305","url":null,"abstract":"<p>Over the past two decades, research utilizing transcriptomics, proteomics, and metabolomics has allowed investigators to look into snapshots of mRNA, protein, and metabolite levels in cells and tissues. These practices have been optimized to look even at a single cell or single nucleus. Further advancements have inspired circadian collections—samples collected every few hours over the course of days—to undergo multi-omics analysis to look at changes in mRNA, protein, and metabolite levels over the course of the day [<span>1, 2</span>]. Even further is a recent publication in Acta Physiologica by Wigger et al. which utilized multi-omics to investigate the time-of-day differences in expression of renal long noncoding RNAs (lncRNAs, Figure 1) [<span>3</span>].</p><p>LncRNAs are as their name describes, long RNA sequences (≥ 200 nucleotides) which are transcribed, but do not code for a protein to be produced. Although they do not code for protein, they can take on many roles in the cell, such as acting as “decoys” to sequester transcription factors or miRNA, “guides” which lead nucleic acids or proteins to specified targets, “scaffolds” to provide structure within complexes, and intracellular “signals” that are influenced by external stimuli [<span>4</span>]. They have also been shown to play a role in disease states in tissues such as the kidney [<span>4</span>]. However, as many lncRNAs remain unannotated in online databases, they can often go overlooked or be thrown out when analyzing transcriptomics data. Additionally, many transcriptomics studies are based on tissues or cells collected at only one time of day, sometimes undefined in the methods.</p><p>Wigger et al. is the first study to investigate time-of-day influence on lncRNA in the kidney through transcriptomics, doing so in male mice from bulk and single-nucleus RNA-Seq data sets [<span>3</span>]. The single-nucleus RNA-Seq dataset was mapped to specific kidney cell types and found that lncRNA was cell-type specific and as reliable as standard mRNA markers to differentiate cell types. Additionally, they looked at how lncRNA expression and rhythms changed in male mice with a conditional kidney tubule specific KO of BMAL1 (cKOt), a protein within the molecular circadian clock which is responsible for regulating the time of transcription of nearly half of the genome. The datasets analyzed were collected at two timepoints (4 h (ZT4) and 16 h (ZT16) after lights-on) and the influence of the molecular circadian clock was investigated by comparing reads from control kidneys to those from cKOt mice. Between these data sets, 5.1% of lncRNAs were differentially expressed between control and cKOt at ZT4 and 10.8% were differentially expressed at ZT16, suggesting a time-of-day influence and circadian regulation of renal lncRNAs, notably in the renal epithelia. To determine if the lncRNAs had a circadian rhythm of expression, they reanalyzed their previously published bulk RNASeq dataset from circad","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862611","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":"AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy","authors":"Wenli Chen,&nbsp;Yanting Lu,&nbsp;Xiangxiang Liu,&nbsp;Bangrui Huang,&nbsp;Daowei Liu,&nbsp;Bilian He,&nbsp;Zhiming Zhao,&nbsp;Qian Wang,&nbsp;Jixi Li,&nbsp;Wenyong Xiong","doi":"10.1111/apha.70304","DOIUrl":"10.1111/apha.70304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Insulin deficiency due to pancreatic β-cell loss and dysfunction is a key event in the pathogenesis of T1DM and a progressive driver of T2DM. This study aims to investigate the role of AS160 in regulating mitochondrial homeostasis and insulin secretion in pancreatic β-cells, and to elucidate the underlying molecular mechanism involving its interaction with HSPA8 and activation of PINK1-Parkin-mediated mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Insulin and AS160 levels in islets were analyzed by immunofluorescence staining. β cell-specific AS160 overexpression mice were generated via lentivirus injection, and their metabolic phenotypes were characterized. In vitro, AS160 was overexpressed or knocked down to assess its impact on cell proliferation, insulin secretion, and mitochondrial function. AS160-interacting proteins were identified by immunoprecipitation-mass spectrometry (IP-MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AS160 expression was significantly decreased in islet and correlated positively with insulin levels in hyperglycemic mice. Specific overexpression of AS160 in β-cells exhibited novel protective effects for the islets and insulin levels in hyperglycemic mice. Mechanistically, AS160 overexpression in β-cells increased mitophagy and preserved mitochondrial biogenesis to maintain healthy mitochondrial homeostasis and insulin secretion. At the molecular level, HSPA8 was identified as a novel AS160-interacting protein that enhances PINK-dependent mitophagy. Knockdown of HSPA8 reversed the overexpression of AS160-induced mitophagy and mitochondrial biogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, this work identifies the AS160-HSPA8 interaction as a key mechanism that sustains mitochondrial homeostasis through regulating mitophagy and mitochondrial biogenesis, thus preserving β-cell mass and function. These findings suggest that AS160 emerges as a pivotal regulator of mitochondrial homeostasis in pancreatic β-cell in vivo.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862644","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":"Finerenone Alleviates Cardiac Microvascular Injury and Neutrophil Extracellular Traps Formation in Diabetic Cardiomyopathy via Regulating AKT1 Phosphorylation","authors":"Su Li,&nbsp;Hexi Zhang,&nbsp;Muyin Liu,&nbsp;Wentao Zhu,&nbsp;Xiaopei Yan,&nbsp;Wenyan Qiu,&nbsp;Yuan Tian,&nbsp;Xiaoyu Lian,&nbsp;Danbo Lu,&nbsp;Zhangwei Chen,&nbsp;Chao Chen,&nbsp;Yuqiong Chen,&nbsp;Juying Qian","doi":"10.1111/apha.70298","DOIUrl":"https://doi.org/10.1111/apha.70298","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus is commonly featured with cardiac microvascular dysfunction and chronic low-grade inflammation, contributing to the progression of diabetic cardiomyopathy (DCM). Finerenone confers cardio-renal protection in diabetic settings, yet its underlying mechanisms remain incompletely defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To explore the beneficial effects and molecular mechanisms of finerenone on cardiovascular dysfunction in uncontrolled DCM from the perspectives of neutrophil extracellular traps (NETs) formation and AKT1 phosphorylation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Finerenone was orally administrated to db/db mice for 24 weeks. Global AKT1 S473A mutation mice and bone marrow chimera mice were subjected to high-fat diet and streptozotocin-induced diabetic mouse model. Proteomics, pharmacological network analysis, and cellular thermal shift assay were employed to identify potential molecular targets of finerenone. Multiple approaches, including immunoblotting and immunofluorescence, were used to detect NETs and related cardiac injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Finerenone treatment significantly improved cardiac and microvascular injury in uncontrolled DCM, as indicated by increased microvascular density, reduced vascular leakage, and alleviated cardiac remodeling. In addition to the mineralocorticoid receptor, AKT1 phosphorylation at S473 was identified as a direct target of finerenone. Finerenone improved AKT1 phosphorylation in endothelial cells to maintain vascular barrier function and reduce damage-associated molecular patterns (DAMPs) release, thereby suppressing polymorphonuclear (PMN) infiltration and NETosis. In contrast, AKT1 phosphorylation in PMN was suppressed by finerenone for NETs inhibition and related cardiac injuries. Similarly, global and cardiac AKT1 S473A mutation accentuated uncontrolled DCM, whereas myeloid AKT1 S473A mutation improved uncontrolled DCM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Finerenone treatment mitigated microvascular dysfunction, DAMPs release, and NETs-associated cardiac injury via balancing AKT1 phosphorylation across different cell types, contributing to its cardiovascular protection in uncontrolled DCM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849236","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":"Innovative Dose–Response Assessment of the Metaboreflex With Indirect Control of Intramuscular Metabolic Perturbation in Humans","authors":"Nabil Kouzkouz,&nbsp;Joris Mallard,&nbsp;Elyse Hucteau,&nbsp;Roland Schott,&nbsp;Xavier Pivot,&nbsp;Guillaume P. Ducrocq,&nbsp;Thomas J. Hureau","doi":"10.1111/apha.70303","DOIUrl":"https://doi.org/10.1111/apha.70303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to evaluate an innovative dose–response approach to assess the metaboreflex with control of intramuscular metabolic perturbation (concept of metaboreflex gain). We also investigated potential sex differences in the metaboreflex using this new approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty participants (15 females) completed one familiarization and two experimental visits to evaluate the method and assess its reproducibility. Each visit involved four consecutive bouts of sustained isometric knee extension at 20% of maximal voluntary force interspersed with 2 min of post-exercise circulatory occlusion (PECO). Intramuscular metabolic perturbation was quantified indirectly via changes in quadriceps twitch force evoked by electrical stimulation of the femoral nerve (∆Q_TW). Metaboreflex gain was calculated as the ratio of ∆mean arterial pressure (∆MAP) during PECO to ∆Q_TW.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found a gradual increase in ∆MAP (<i>p</i> &lt; 0.0001) that was linearly correlated with the gradual decrease in ∆Q_TW (<i>p</i> &lt; 0.0001) during the exercise bouts (<i>r</i>² = 0.93; <i>p</i> = 0.037). Bland–Altman analysis showed a mean bias of 0.3 ± 0.5 for metaboreflex gain. Males exhibited greater metaboreflex to PECO than females when assessed “classically” with no control of ∆Q_TW (∆MAP; 49.1% ± 17.9% vs. 36.5% ± 8.7%; <i>p</i> = 0.020), whereas there was no sex difference when assessed using the metaboreflex gain (∆MAP/∆Q_TW; 1.3 ± 0.6 vs. 1.8 ± 1.3; <i>p</i> = 0.325). The metaboreflex gain was not consistent across exercise bouts, showing that contrasting conclusions might emerge between two single assessments performed at different levels of metaboreflex activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the critical need for using a dose–response relationship while accounting for neuromuscular fatigue as a proxy for the metabolic stimulus when assessing the muscle metaboreflex in humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Clinical trials registration number: NCT06775119</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849227","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":"Repeated Moderate and Severe Heat Exposure Has Divergent Effects on Skeletal Muscle Mitochondrial, Proteostatic and Neuromuscular Outcomes in Mice","authors":"Cansu Yakin,&nbsp;Cihan Suleyman Erdogan,&nbsp;Fatma Ozge Tuncel,&nbsp;Yunus Kosif,&nbsp;Bayram Yilmaz","doi":"10.1111/apha.70301","DOIUrl":"https://doi.org/10.1111/apha.70301","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Repeated heat exposure may promote adaptive remodeling or cumulative tissue burden depending on thermal dose, but its graded molecular and functional consequences during recovery remain unclear. We examined whether repeated moderate (39°C) and severe (41°C) whole-body hyperthermia produce distinct skeletal muscle trajectories involving mitochondrial dynamics, proteostasis, contractile gene programming, and motor behavior.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult male Swiss mice underwent 15-min daily whole-body heat exposure for 7 days at 39°C or 41°C core temperature and were assessed immediately or after 7 days of recovery. Motor and behavioral outcomes were evaluated using open-field, elevated plus maze, grip strength, and rotarod tests. Gastrocnemius muscle was analyzed by qRT-PCR, immunoblotting, and immunofluorescence for mitochondrial biogenesis, dynamics, mitophagy, proteostasis, and contractile phenotype markers. Cerebellar HSP60/HSP70 immunoreactivity and serum corticosterone were also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At 39°C, recovery induced coordinated mitochondrial biogenesis and balanced fission-fusion transcript upregulation. At 41°C, acute <i>Ppargc1a</i> induction (<i>p</i> &lt; 0.01) was followed by recovery-phase mitophagy and oxidative-response gene upregulation. Gastrocnemius ERK phosphorylation increased preferentially during 39°C exposure (<i>p</i> &lt; 0.05). HSP60 progressively declined across recovery groups, whereas HSP70 increased only after 41°C recovery (<i>p</i> &lt; 0.05). Grip-related neuromuscular performance was impaired at 41°C in both phases (<i>p</i> &lt; 0.05), while rotarod performance remained intact. Cerebellar HSP70 was strongly suppressed by heat exposure (<i>p</i> &lt; 0.0001) and partially restored after 39°C recovery. Principal component analysis without group labels reproduced this divergence, yielding a dose × phase interaction axis (<i>p</i> = 5.7 × 10⁻⁷).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Moderate hyperthermia supports adaptive mitochondrial remodeling, whereas severe hyperthermia promotes stress-related quality control, proteostatic strain, contractile suppression, and reduced grip-related neuromuscular performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816593","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":"ITCH-Mediated Ubiquitination and Degradation of THBS1: A Key Mechanism for Enhancing Mitochondrial Biogenesis and Alleviating Mouse Skeletal Muscle Atrophy","authors":"Wan Yu,&nbsp;Yanteng Wang,&nbsp;Na Li,&nbsp;Difei Wang","doi":"10.1111/apha.70299","DOIUrl":"10.1111/apha.70299","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Skeletal muscle atrophy is tightly associated with maladaptive alterations in mitochondrial function and morphology. Itchy E3 ubiquitin-protein ligase (ITCH) modulates mitochondria, and thrombospondin 1 (THBS1) positively regulates muscle atrophy, but their roles in muscle atrophy are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A muscle atrophy model was established in C57BL/6 mice via daily intraperitoneal injection of dexamethasone (Dex, 20 mg/kg). ITCH overexpression in skeletal muscle was achieved by adeno-associated virus serotype 9 injection. C2C12 cells were treated with 50 μM Dex to mimic in vitro muscle atrophy. Skeletal muscle atrophy in mice was evaluated using hematoxylin–eosin staining and immunofluorescence staining. Mitochondrial damage was assessed via transmission electron microscopy, succinate dehydrogenase staining, and JC-1 staining. Immunoprecipitation-liquid chromatography/mass spectrometry, molecular docking, and co-immunoprecipitation were used to investigate the interaction between ITCH and THBS1. Phosphoproteomics analysis was performed to detect the THBS1 downstream proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dex treatment downregulated ITCH expression in skeletal muscle. ITCH overexpression increased body weight, muscle mass, and muscle strength, downregulated the expression of atrophy-related genes (Atrogin-1, Mstn, MuRF-1), and promoted mitochondrial biogenesis. The results of the C2C12 cells were consistent with those obtained in vivo. Proteomic profiling and Co-IP confirmed ITCH–THBS1 interaction and subsequent THBS1 ubiquitination. THBS1 knockdown reduced the expression of Atrogin-1 and MuRF-1 and inhibited the phosphorylation of JUN and Map3k7, whereas THBS1 overexpression reversed the ITCH-mediated improvement in mitochondrial biogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ITCH enhances mitochondrial biogenesis and mitigates Dex-induced muscle atrophy by promoting the ubiquitin-dependent degradation of THBS1 and subsequent inhibition of downstream JUN/Map3k7 phosphorylation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838626","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":"Immune-Induced Fever and Psychogenic Hyperthermia Can Occur Independently of Uncoupling Protein 1-Mediated Brown Adipose Tissue Thermogenesis","authors":"Takashi Matsuwaki,&nbsp;Wakana Harigai,&nbsp;Vladimir Maksimov,&nbsp;Yutaro Nakayama,&nbsp;Kazuyuki Uchida,&nbsp;James K. Chambers,&nbsp;Keitaro Yamanouchi,&nbsp;Anna Eskilsson,&nbsp;Anders Blomqvist","doi":"10.1111/apha.70300","DOIUrl":"10.1111/apha.70300","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Brown adipose tissue thermogenesis is widely considered an important effector mechanism in fever and emotionally induced hyperthermia (psychogenic fever), and increases in interscapular temperature are commonly interpreted as evidence of brown adipose tissue activation. Yet direct evidence for this interpretation remains limited and conflicting. Here, we tested these assumptions using complementary genetic and surgical approaches in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated uncoupling protein 1 knockout rats, in which canonical brown adipose tissue thermogenesis is abolished, and examined body temperature responses to systemic inflammation induced by lipopolysaccharide and to emotional stressors, including restraint and cage exchange. In separate experiments, interscapular brown adipose tissue was surgically removed in wild-type rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite profound impairment of cold- and β_₃-adrenergic-induced thermogenesis, uncoupling protein 1 deletion did not affect lipopolysaccharide- or stress-induced increases in core or interscapular temperature. Likewise, removal of interscapular brown adipose tissue did not alter the interscapular temperature response. Thus, increases in interscapular temperature occurred in the absence of both uncoupling protein 1 and interscapular brown adipose tissue. Consistent with these findings, immune challenge and emotional stress induced little or no change in thermogenic gene expression and had minimal effects on tissue mass, in contrast to robust activation by β_₃-adrenergic stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Fever and psychogenic hyperthermia in rats do not require uncoupling protein 1-mediated brown adipose tissue thermogenesis. Furthermore, increases in interscapular temperature are not necessarily indicative of brown adipose tissue thermogenesis, challenging a widely held interpretation of these phenomena.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13505244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811401","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":"Reduced Expression of Magnesium Transport Proteins in the Distal Convoluted Tubule of Clcnkb-Deficient Mice May Explain Urinary Magnesium Wasting in Classical Bartter Syndrome","authors":"Marleen L. A. Kortenoeven,&nbsp;Milos Bogdanovic,&nbsp;Ida Appel,&nbsp;Karsten Skjødt,&nbsp;Ernst-Martin Fuchtbauer,&nbsp;Kirsten Madsen,&nbsp;Lars Lund,&nbsp;Régine Chambrey,&nbsp;Dominique Eladari,&nbsp;R. Todd Alexander,&nbsp;Christian A. Hübner,&nbsp;J. Christopher Hennings,&nbsp;Henrik Dimke","doi":"10.1111/apha.70295","DOIUrl":"https://doi.org/10.1111/apha.70295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The kidney thick ascending limb (TAL) plays a key role in the transport of sodium, chloride, potassium, calcium, and magnesium. Bartter syndrome is a hypokalemic, salt-losing tubulopathy caused by impaired TAL function. Pathogenic variants in <i>SLC12A1</i> or <i>KCNJ1</i> cause antenatal Bartter syndrome, and variants in <i>CLCNKB</i> result in classical Bartter syndrome. Although all variants impair TAL electrolyte transport, their effects on mineral handling differ. In contrast to antenatal forms, classical Bartter syndrome is frequently associated with hypomagnesemia, a feature also found in Gitelman syndrome resulting from pathogenic variants in <i>SLC12A3</i>, expressed in the distal convoluted tubule (DCT). The mechanisms underlying these distinct clinical phenotypes are not understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Clcnkb-</i> and <i>Slc12a3</i>-deficient mice as well as human kidneys were investigated. The abundance and localization of electrolyte and mineral transporters and stereological parameters were assessed by immunohistochemistry. Gene and protein expression was determined in <i>Clcnkb</i>-deficient mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In human kidney, both ClC-K channels and their essential subunit Barttin were found in TAL, DCT, and collecting system. <i>Clcnkb</i>-deficient mice showed complete ablation of <i>Clcnkb</i> and reduced DCT and connecting tubule volumes. Furthermore, DCT magnesium channels and select basolateral magnesium transporters were markedly reduced in <i>Clcnkb</i>-deficient mice, similar to <i>Slc12a3</i>-deficient mice. In contrast, the overall abundance of calcium transport proteins was largely preserved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ClC-K channels are expressed in the TAL and DCT in mouse and human kidneys. <i>Clcnkb</i> ablation reduces TRPM magnesium channel expression and DCT tubule volume, providing a likely explanation for the frequently observed hypomagnesemia in classical Bartter syndrome.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785032","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":"Free Fatty Acids Carried by Lipoproteins: Revisiting the Overlooked Cargo","authors":"Gregory C. Henderson,&nbsp;Kimberly K. Buhman,&nbsp;Keigo Tomoo","doi":"10.1111/apha.70296","DOIUrl":"https://doi.org/10.1111/apha.70296","url":null,"abstract":"<p>Free fatty acids (FFAs) are hydrophobic and therefore cannot enter the bloodstream at appreciable levels unless they are solubilized by FFA carriers. Albumin has been appreciated for years as the major FFA carrier, but it is not the only carrier. While the cholesterol and triacylglycerol components of lipoproteins are measured clinically, there are other bioactive lipids present in lipoproteins as well. There is strong evidence showing that multiple lipoprotein classes carry FFAs, and some evidence indicates potential physiological roles of lipoprotein-bound FFAs. Apolipoproteins and other lipoprotein-associated proteins may be responsible for FFA binding to lipoprotein particles, as lipoproteins contain numerous proteins that are predicted to have multiple FFA binding sites. Lipoproteins isolated from plasma contain FFAs, and the FFA loading appears to be driven in part by mass action when the FFA level is elevated as well as by low albumin abundance in cases of severe hypoalbuminemia. When the FFA levels rise on lipoproteins, through effects on cholesterol ester transfer protein, the lipoprotein profile may be altered. FFA binding to lipoproteins may also protect the lipoproteins from oxidative damage. The contribution of lipoproteins to FFA flux through the circulation is less clear but may play a particularly important role when albumin expression is low to drive the recruitment of this secondary FFA carrier system. In recent decades research progress has slowed in this area, leaving major knowledge gaps to address. The remaining need for research is discussed, and the physiological implications of lipoprotein-bound FFAs are discussed in this review.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785041","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":"Immature Neutrophil Phenotype and Enhanced Myeloperoxidase in Male Patients With Chronic Kidney Disease and Cardiovascular Comorbidity","authors":"Sonja Vondenhoff,&nbsp;Alessandra Antwerpen,&nbsp;Carolina Victoria Cruz Junho,&nbsp;Philipp Martin,&nbsp;Sina Hourtz,&nbsp;Jinmi Zou,&nbsp;Berkan Kurt,&nbsp;Carolin Haas,&nbsp;Susanne Fleig,&nbsp;Corinna Schulte,&nbsp;Jane Lauxen,&nbsp;Martina Wessiepe,&nbsp;Ulrike Späte-Schulze,&nbsp;Rafael Kramann,&nbsp;Jürgen Floege,&nbsp;Oliver Soehnlein,&nbsp;Joachim Jankowski,&nbsp;Claudia Goettsch,&nbsp;Yvonne Döring,&nbsp;Florian Kahles,&nbsp;Nikolaus Marx,&nbsp;Constance C. F. M. J. Baaten,&nbsp;Heidi Noels","doi":"10.1111/apha.70290","DOIUrl":"https://doi.org/10.1111/apha.70290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Patients with chronic kidney disease (CKD) have an increased cardiovascular risk. Since neutrophils and neutrophil-borne proteins contribute to cardiovascular disease, we analyzed the neutrophil phenotype in patients with CKD who presented with a spectrum of cardiovascular comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood from two independent cohorts of male patients with moderate to advanced CKD recruited through the cardiology or nephrology unit was analyzed for neutrophils maturation and activation markers using flow cytometry compared to healthy controls. The formation of neutrophil-extracellular traps was assessed using isolated neutrophils. Plasma levels of neutrophil-borne proteins (neutrophil elastase, myeloperoxidase, and S100A8/A9), plasma inflammatory markers and cardiovascular disease characteristics were compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both cohorts of CKD patients showed reduced neutrophil surface expression of maturation marker CD10 and higher plasma levels of myeloperoxidase compared to controls. No significant differences were observed in neutrophil surface activation markers in either baseline or stimulated conditions, or in the formation of neutrophil extracellular traps ex vivo. Although CKD patients presented with variable degrees of systemic inflammation and cardiovascular comorbidities, the immature neutrophil phenotype (low CD10) was not associated with either inflammatory status (CRP, IL6) or NT-proBNP levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Male cardiorenal patients with moderate to advanced CKD do not show altered neutrophil surface activation markers or ex vivo activation potential per se. Yet, they display a more immature neutrophil phenotype and higher circulating neutrophil-borne myeloperoxidase as observed across a range of systemic inflammation degrees. This could potentially contribute to the overall increased cardiovascular risk in CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 9","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784011","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}