Acta Physiologica最新文献

{"title":"Functional Training Mitigates Reduced Circulating Indole-3-Lactate Levels in Persons With Relapsing–Remitting Multiple Sclerosis","authors":"Tiffany Wences Chirino,&nbsp;Frederike Adammek,&nbsp;Sergen Belen,&nbsp;Matteo Winker,&nbsp;Sebastian Proschinger,&nbsp;Annette Rademacher,&nbsp;Marit L. Schlagheck,&nbsp;Alexander Schenk,&nbsp;Marie Kupjetz,&nbsp;David Walzik,&nbsp;Clemens Warnke,&nbsp;Marcel Reuter,&nbsp;Friederike Rosenberger,&nbsp;Tim Meyer,&nbsp;Adrian McCann,&nbsp;Per Magne Ueland,&nbsp;Niklas Joisten,&nbsp;Philipp Zimmer","doi":"10.1111/apha.70166","DOIUrl":"10.1111/apha.70166","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Indoles are tryptophan (Trp)-derived metabolites that are produced by the gut microbiota and may influence the gut-microbiota-brain axis in multiple sclerosis (MS). Indole-3-lactate (ILA) is reduced in persons with MS and improves MS clinical scores in animal models via its anti-inflammatory remyelinating properties. The ILA/indole-3-acetate (IAA) (ILA/AA) index is considered a neuroprotection index. Physical exercise and diet can modify gut microbiota and indole metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This secondary analysis of a randomized control trial aimed to assess the effects of acute and chronic exercise on serum indoles in relapsing–remitting MS (RRMS). Thirty-one RRMS patients (≥ 70% session attendance) completed a 10 week multimodal functional training (60 min, 3×/week) vs. a waitlist control group. Blood samples were collected at baseline and compared to a matched healthy control group, and after 10 weeks for the assessment of chronic effects. Additionally, acute effects of a single bout of exercise were assessed with a blood sample before, during, and immediately after one interim training session. Serum indole concentrations were measured using LC–MS/MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline indole levels in RRMS patients differed from those of matched healthy controls, and reduced ILA levels were observed. The 10 week intervention increased the ILA/IAA index, while a single exercise bout induced an increase in both ILA and ILA/IAA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Multimodal functional training over 10 weeks led to an improved ILA/IAA index suggesting a neuroprotective shift in gut microbiota composition, and a single bout acutely increases the circulating level of ILA. Study registration number: DRKS00017091.</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/PMC12852534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146091541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Secondary Motor Cortex Encodes Aversive Signals and Exerts an Inhibitory Control of Motor Sequence Learning in Mice","authors":"Xinran Pan,&nbsp;Yan Li,&nbsp;Qionghui Cai,&nbsp;Yang Ruan,&nbsp;Linshan Huang,&nbsp;Shang Zhou,&nbsp;Zhimo Yao,&nbsp;Qin Wang,&nbsp;Liping Zhang,&nbsp;Jiang-Fan Chen,&nbsp;Yan He","doi":"10.1111/apha.70164","DOIUrl":"10.1111/apha.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The secondary motor cortex (M2) is engaged in behavioral planning, movement preparation, and the execution of complex motor sequences in a specific order. However, the nature of neuronal signals encoded by M2 neurons (i.e., reward or aversive) and their behavioral effects on motor sequence learning remain unclear. This study aimed to elucidate the nature of these signals and their regulatory roles in motor behavior.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We combined in vivo fiber photometry with optogenetics in mice undergoing conditioning paradigms and motor sequence learning tasks. Calcium signals were recorded from general M2 neurons, PV⁺ interneurons, and VgluT2⁺ projection neurons in response to reward (sucrose) and aversive (foot-shock, LiCl) stimuli. Furthermore, M2 neurons were optogenetically activated during reward delivery in the motor sequence learning task. The behavioral outcomes were further dissected using progressive ratio and open-field tests to distinguish between motivational and direct motor effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>M2 neurons, including PV⁺ and VgluT2⁺ subpopulations, consistently encoded aversive signals, exhibiting negative responses to rewards and positive responses to aversive stimuli. Crucially, optogenetic activation of M2 neurons during reward delivery significantly suppressed the initiation and execution of motor sequences. This behavioral impairment was driven by a reduction in motivational vigor, indicated by decreased lever pressing and a lower break point in the progressive ratio test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>M2 neurons encode aversive signals that functionally devalue rewards, thereby reducing motivation and inhibiting motor sequence learning. These results identify M2 as a critical node in neural circuits that adaptively gates motor output based on negative motivational valence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016710","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":"Non-Hebbian Long-Term Depression at VIP Interneuron Inputs Selectively Tunes Inhibition in Disinhibitory Circuits of Mouse Hippocampus","authors":"Jadwiga Jabłońska,&nbsp;Grzegorz Wiera,&nbsp;Jerzy W. Mozrzymas","doi":"10.1111/apha.70162","DOIUrl":"10.1111/apha.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Control of synaptic inhibition at the network level is essential for neuronal computation; however, the mechanism by which inhibitory I → I synapses between interneurons adjust their strength remains unclear. Here, we describe a non-Hebbian form of inhibitory long-term depression (iLTD) that operates at vasoactive intestinal peptide (VIP) interneuron inputs onto stratum oriens interneurons in the hippocampal CA1 region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-cell recordings of oriens interneurons combined with optogenetic VIP-positive input activation in mouse hippocampal slices.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Repeated postsynaptic burst firing alone was sufficient to induce a persistent weakening of VIP-mediated I → I inhibitory transmission onto oriens interneurons. This plasticity was insensitive to presynaptic stimulation paired with postsynaptic burst spiking, confirming its non-Hebbian character. The observed iLTD required postsynaptic calcium influx through L- and T-type voltage-gated calcium channels but was independent of endocannabinoid signaling, indicating a postsynaptic mechanism. To better define the cell-specificity of plastic changes at I → I synapses on oriens interneurons, we compared these findings with plasticity induced by analogous protocols at inhibitory synapses formed by two major interneuron types (parvalbumin- and somatostatin-positive) onto pyramidal neurons. These synapses, however, followed classical and subtype-specific Hebbian spike-timing–dependent rules and were unaffected by postsynaptic burst activity. Notably, physiologically relevant theta-burst stimulation of excitatory inputs to oriens interneurons induced heterosynaptic I → I iLTD and increased the excitatory/inhibitory balance in these cells, thereby enhancing their recruitment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings identify a cell-type-specific, activity-history–dependent rule of inhibitory I → I plasticity that weakens disinhibition in a non-Hebbian manner, revealing a novel physiological mechanism that modulates gain within hippocampal microcircuits.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996842","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":"Mechanisms of Skeletal Muscle Mass Regulation and Muscle Memory","authors":"Kristian Gundersen,&nbsp;Jo C. Bruusgaard,&nbsp;Einar Eftestøl","doi":"10.1111/apha.70152","DOIUrl":"10.1111/apha.70152","url":null,"abstract":"<div>\u0000 \u0000 <p>Changes in muscle mass and force are mainly related to changes in fiber size. In eukaryotes, DNA-content and cell size are generally correlated, suggesting the existence of a DNA-template limitation. This might be particularly important in the skeletal muscle fiber syncytia, which contain 30%–50% less DNA per cytoplasmic volume than most cells. Muscle fibers display a correlation between fiber size and myonuclear number, and genetically reducing the number reduces the size. Even so, the cytoplasmic volume per nucleus is larger in larger cells, demonstrating some flexibility in each nucleus' ability to “produce volume.” De novo hypertrophy leads to accrual of myonuclei, which do not seem to be lost; the “extra” nuclei might serve as a mechanism for muscle memory. A complementary hypothesis is that muscle memory relies on each nucleus' ability to provide protein related to persistent/long-lasting epigenetic traces. A few epigenetically altered loci have been suggested, but there is currently no consensus between various studies as to which these are.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996866","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":"Activation of TGR5 Alleviates Renal Fibrosis by Promoting NEDD4L-Mediated p-Smad2/3 Ubiquitination","authors":"Meng Li,&nbsp;Luosha Long,&nbsp;Xiaoduo Zhao,&nbsp;Xi Yuan,&nbsp;Minghui Wang,&nbsp;Jinyi Lin,&nbsp;Long Xu,&nbsp;Xinyan Wu,&nbsp;Ruiqi Bai,&nbsp;Suchun Li,&nbsp;Weidong Wang,&nbsp;Wei Chen,&nbsp;Lihe Lu,&nbsp;Chunling Li","doi":"10.1111/apha.70163","DOIUrl":"10.1111/apha.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Renal fibrosis is a major contributor to chronic kidney disease (CKD) progression and eventual organ failure. G protein-coupled bile acid receptor 1 (TGR5) was previously shown to have beneficial effects on kidney diseases. The current study aimed to investigate whether TGR5 activation prevents kidney fibrosis and to clarify the underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TGR5 expression was examined in human fibrotic kidneys. Two animal models of renal fibrosis were used: unilateral ureteral obstruction (UUO) and unilateral ischemia–reperfusion injury with contralateral nephrectomy (uIRIx) in wild-type and <i>TGR5</i> knockout mice. Renal histology, extracellular matrix (ECM) deposition, and renal function were examined. In vitro studies were performed on human proximal tubular HK2 cells by treating them with transforming growth factor-β1 and TGR5 agonists/antagonists.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TGR5 was significantly downregulated in fibrotic human kidneys. In both UUO and uIRIx models, TGR5 activation by lithocholic acid alleviated renal fibrosis, reduced ECM deposition, and improved kidney function. Conversely, <i>Tgr5</i> knockout in mice exacerbated fibrotic injury. Mechanistically, TGR5 activation prevented fibrosis development, probably by enhancing NEDD4L-mediated ubiquitination and degradation of phosphorylated Smad2/3 by inhibiting the upstream PI3K–SGK1 pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TGR5 activation protects against renal fibrosis by inhibiting the PI3K–SGK1–NEDD4L axis and promoting p-Smad2/3 degradation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970346","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":"The Calcium-Binding Protein S100A10 (p11) Is Required for Normal Motor Performance by Regulating Vesicle Dynamics at Excitatory Synapses","authors":"Esther Vilches-Herrando,&nbsp;Guillermo Rodríguez-Bey,&nbsp;Rosendo G. Hernández,&nbsp;Ángela Gento-Caro,&nbsp;Ángel M. Pastor,&nbsp;Antonio Campos-Caro,&nbsp;David González-Forero,&nbsp;Bernardo Moreno-López","doi":"10.1111/apha.70158","DOIUrl":"10.1111/apha.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Identifying interactors in sensorimotor processing and neurotransmission remains a current challenge for understanding neural information processing and brain function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To evaluate the role of p11 in sensorimotor processing and excitatory synaptic neurotransmission, neuron-specific lentivirus-directed p11 silencing, small interfering RNA (siRNA_p11)-induced p11 deletion, unitary extracellular recordings of hypoglossal motor neurons (HMNs), western blot, co-immunoprecipitation, multiple immunolabeling, proximity ligation (PLA) assays, electron microscopy, and whole-cell patch-clamp recording of AMPA receptor–mediated excitatory postsynaptic currents in adult and/or neonatal rat HMNs were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>p11 knockdown depressed baseline and chemoreceptor-modulated inspiratory-related activity in HMNs. Co-immunoprecipitation and PLA assays indicated that p11 interacts with Munc13-1, a presynaptic active zone (AZ) protein for vesicle priming, presumably at excitatory inputs in the hypoglossal nucleus. Interference with p11 resulted in Munc13-1 downregulation, reduction in AZ length, and increased vesicle accumulation at excitatory boutons on HMNs, without affecting the number of docked vesicles at the AZ. p11 knockdown robustly reduced the synaptic strength of excitatory neurotransmission incoming to HMNs by affecting both the synchronous and asynchronous phases of neurotransmitter release. The decrease in synaptic strength was concurrent with a reduction in the size of the “functional” pool of readily releasable (RRP) vesicles and with the slowing down of the vesicle recruitment rate to replenish RRP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>p11 is proposed as a relevant mediator in the neurotransmitter release by regulating vesicle dynamics at central excitatory synapses. Here, p11 is highlighted as a multifaceted factor involved in neurotransmission and synaptic plasticity and, therefore, central for neural information processing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12793959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950943","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":"Acyl-CoA Binding Protein in White and Brown Adipose Tissue Is Dispensable for Systemic Energy Metabolism in Mice","authors":"M. F. Nørremark,&nbsp;R. Petersen,&nbsp;P. M. M. Ruppert,&nbsp;E. S. Jul,&nbsp;T. K. Doktor,&nbsp;R. Nielsen,&nbsp;J. F. Kappel,&nbsp;S. Larsen,&nbsp;J. W. Kornfeld,&nbsp;S. Mandrup,&nbsp;B. S. Andresen,&nbsp;J. Havelund,&nbsp;D. Neess,&nbsp;N. J. Færgeman","doi":"10.1111/apha.70159","DOIUrl":"10.1111/apha.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Acyl-CoA binding protein plays a vital role in lipid metabolism by mediating the intracellular flux and utilization of long-chain acyl-CoAs. We generated an adipocyte-wide ACBP knockout mouse and a brown adipose tissue-specific ACBP knockout mouse to investigate ACBP function in adipose tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male mice with conditional targeting of the <i>Acbp</i> gene in adipose tissue (Adipoq-<i>Acbp</i>^{<i>−/−</i>}) or brown adipose tissue (Ucp1-<i>Acbp</i>^{<i>−/−</i>}) were generated by crossing <i>Acbp</i>^{<i>flox/flox</i>} mice with transgenic mice expressing Cre recombinase under the control of the adiponectin (<i>Adipoq-Cre</i>) or uncoupling protein 1 (<i>Ucp1-Cre</i>) promoter, respectively. Systemic energy expenditure was assessed by indirect calorimetry. Body composition was examined using nuclear magnetic resonance. Primary brown and white preadipocytes were isolated to examine their ability to differentiate to mature adipocytes. Lipid composition of adipose tissues was examined by lipidomics. Global changes in gene expression in adipose tissues were examined by RNA sequencing. Tissue respiration was determined using high-resolution respirometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate that loss of ACBP in adipose tissue does not affect body weight, fat and lean mass, food intake and systemic energy expenditure, even under cold stress. Global gene expression analysis shows only minor changes in gene expression, whereas lipidomic profiling reveals a subtle increase in acyl-carnitine levels in brown adipose tissue. Lipolytic activity in white adipose tissue as well as plasma glycerol, nonesterified fatty acid and triacylglycerol levels remained unaffected. In addition, no changes in mitochondrial respiration in BAT were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that ACBP is dispensable for adipose tissue function and systemic energy metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12791089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950960","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":"Glucocorticoid Feedback on the Adult Suprachiasmatic Clock","authors":"Dominique Sage-Ciocca,&nbsp;Etienne Challet","doi":"10.1111/apha.70156","DOIUrl":"10.1111/apha.70156","url":null,"abstract":"&lt;p&gt;Biological processes are structured over 24 h by endogenous time-keeping systems, called circadian clocks that are reset daily by external (e.g., ambient light) and internal synchronizers (e.g., glucocorticoids (GC)). The suprachiasmatic nuclei of the hypothalamus (SCN) are a key structure of the circadian timing system because they contain a master circadian clock that controls the daily timing of most behavioral and physiological functions, including the sleep–wake cycle and hormonal rhythms. In this issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Sládek et al. [&lt;span&gt;1&lt;/span&gt;] provide convincing experimental evidence for the presence of functional GC receptors (GR) in the SCN of adult rats and mice.&lt;/p&gt;&lt;p&gt;GC synthesized in the adrenal glands are mostly known for their roles in stress responses, metabolism, and immunity. However, their daily rhythmic secretion with peaks around wake-up time provides for an important internal synchronizer of the circadian system, especially for peripheral tissues such as adipose tissue and liver, and brain areas like the raphe nuclei and central amygdala [&lt;span&gt;2&lt;/span&gt;]. During development, the SCN of fetuses that express high levels of GR can be synchronized by maternal GC [&lt;span&gt;3, 4&lt;/span&gt;]. Until now, it was thought that GR is no longer expressed in adult SCN cells [&lt;span&gt;5, 6&lt;/span&gt;], leading to the prevailing view that GC and associated stress responses do not feedback directly to the master clock in adulthood. Accordingly, modulatory effects of glucocorticoids on the master clock functions, notably its synchronization to ambient light, were considered to be indirectly mediated via sensitive cerebral targets projecting to the SCN, like the raphe nuclei [&lt;span&gt;2, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;By demonstrating high expression of GR and of &lt;i&gt;Nr3c1&lt;/i&gt; encoding GR in the adult SCN cells, Sládek and collaborators challenge a current dogma in the field of circadian research. Depending on the detection method used (i.e., RT-qPCR, in situ hybridization, immunohistochemistry, western blot), the relative level of expression may vary considerably from one study to another. Nevertheless, the links between levels of expression of GR, their functionality and the physiological effects of GC on the studied structure should always be questioned. Here the authors demonstrate that in vivo administration of dexamethasone (DEX), a synthetic glucocorticoid, activates the transcription of GC target genes, such as &lt;i&gt;Gilz&lt;/i&gt; and &lt;i&gt;Sgk1&lt;/i&gt;, within the adult SCN [&lt;span&gt;1&lt;/span&gt;]. From a physiological perspective, these observations reveal that SCN cells are directly sensitive to GC and receive direct feedback information from circulating GC. These new findings are consistent with the modulation of GR expression levels in the SCN by circulating GC concentrations [&lt;span&gt;8&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Sládek et al. [&lt;span&gt;1&lt;/span&gt;] also confirm that in vitro DEX treatment can induce phase-shifts in the fetal SCN clock, but not in the mature master clock. Interesting","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950963","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":"Human Skeletal Muscle Mitochondria Responses to Weight Loss Induced by Bariatric Surgery or Lifestyle Intervention","authors":"Birgitta W. van der Kolk,&nbsp;Sini Heinonen,&nbsp;James W. White,&nbsp;Anita Wagner,&nbsp;Jari E. Karppinen,&nbsp;Sina Saari,&nbsp;Maheswary Muniandy,&nbsp;Simo Metsikkö,&nbsp;Eugène T. Dillon,&nbsp;Per-Henrik Groop,&nbsp;Tuure Saarinen,&nbsp;Carel W. Le Roux,&nbsp;Kirsi A. Virtanen,&nbsp;Neil G. Docherty,&nbsp;Eija Pirinen,&nbsp;Anne Juuti,&nbsp;Kirsi H. Pietiläinen","doi":"10.1111/apha.70150","DOIUrl":"10.1111/apha.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We investigated how weight loss induced by bariatric surgery or lifestyle intervention affects skeletal muscle mitochondrial metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied two weight-loss cohorts: RYSA (BMI ≥ 35 kg/m²; <i>n</i> = 39, including 18 with diabetes) undergoing bariatric surgery, and CRYO (BMI ≥ 30 kg/m²; <i>n</i> = 19) undergoing a lifestyle intervention with a low-calorie diet. Assessments were performed at 5–6 and 12 months and included muscle proteome (LC–MS/MS), mitochondrial biogenesis by mtDNA amount (qPCR), number and morphology (transmission electron microscopy) in both cohorts, and mitochondrial oxidative capacity (high-resolution respirometry) in the surgery cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both cohorts achieved clinically meaningful weight loss, greater following surgery (24.4% vs 9.0% at 12 months). Per 1% weight loss, bariatric surgery was associated with significant downregulation of glycolysis pathways at 12 months. OXPHOS complex subunit proteins were associated with upregulation in individuals without diabetes but downregulation in those with diabetes. Lifestyle intervention was associated with downregulated OXPHOS complex subunits at 5 months. Mitochondrial morphology remained unchanged, while mtDNA amount correlated negatively with weight loss percentage in both cohorts. In the surgery cohort, complex I and complex I + II-mediated respiration increased 3.2- and 2.9-fold at 12 months, reflecting improved oxidative capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Bariatric surgery was associated with increased skeletal muscle mitochondrial respiration despite unchanged morphology and reduced mtDNA amount, whereas lifestyle-induced weight loss showed a transient downregulation of OXPHOS-related proteins with other mitochondrial markers remaining stable. Surgery-induced weight loss may reflect improved mitochondrial efficiency in skeletal muscle, potentially influenced by diabetes status. Long-term functional mitochondrial adaptations after weight loss require future studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>RYSA: ClinicalTrials.gov ID NCT02882685; CRYO: ClinicalTrials.gov ID NCT01312090</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931345","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":"Distinct Roles of SLC26A3 and CFTR in Surface pH Regulation and Bicarbonate Secretion in Human Intestinal Epithelium","authors":"Mahdi Amiri,&nbsp;Azam Salari,&nbsp;Ursula Seidler","doi":"10.1111/apha.70157","DOIUrl":"10.1111/apha.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Colonic bicarbonate secretion is mediated by the chloride/bicarbonate exchanger SLC26A3 and the cystic fibrosis transmembrane conductance regulator (CFTR). Dysfunction of either causes luminal acidosis, altered mucus properties, and inflammation. While physical and functional interactions have been demonstrated in heterologous systems, their relationship in native epithelium is not fully established. We investigated the distinct roles of SLC26A3 and CFTR using human intestinal organoids with inducible SLC26A3 overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human colonic and rectal organoids from healthy controls and cystic fibrosis patients with F508del mutations were studied in the proliferative state with high endogenous CFTR expression and inducible SLC26A3 overexpression. Real-time surface pH measurements, electrophysiological analysis, forskolin-induced swelling assays, and confocal microscopy were employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Steady-state surface pH was lower in CF versus healthy organoids (7.23 ± 0.03 vs. 7.34 ± 0.03). SLC26A3 overexpression normalized surface pH in CF organoids and CFTR-inhibited organoids, equalizing responses between genotypes. SLC26A3 overexpression corrected abnormal morphology and significantly improved intracellular MUC2 distribution in CF organoids. However, SLC26A3 did not restore fluid secretion in CF organoids or enhance CFTR-mediated electrogenic anion secretion in Ussing chambers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SLC26A3 and CFTR perform distinct yet complementary functions. SLC26A3 dominates surface pH regulation and maintains bicarbonate efflux independently of CFTR, while CFTR drives agonist-stimulated fluid secretion. SLC26A3's ability to restore pH homeostasis and normalize mucin intracellular distribution in CF organoids demonstrates its critical importance for maintaining colonic mucosal health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909603","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}