American journal of physiology. Gastrointestinal and liver physiology最新文献

{"title":"The gut microbiota metabolite isovalerate enhances the epithelial barrier function in cell monolayers derived from porcine ileum organoids.","authors":"Martin Beaumont, Cláudia M Vicente, Cristina Plata-Calzado, Corinne Lencina, Elisabeth Jones, Stéphanie Lecuelle, Tristan Chalvon-Demersay","doi":"10.1152/ajpgi.00193.2025","DOIUrl":"10.1152/ajpgi.00193.2025","url":null,"abstract":"<p><p>The gut microbiota produces numerous metabolites that influence the epithelial barrier function. Bacterial catabolism of amino acids produces a wide variety of metabolites whose effects on the intestinal epithelium remain to be identified. In this study, we investigated the effects of amino acid-derived metabolites (isovalerate, isobutyrate, 2-methylbutyrate, 5-aminovalerate, cadaverine, putrescine, and tryptamine) in cell monolayers derived from porcine ileum organoids. Our results show that the branched-chain fatty acid (BCFA) isovalerate improved the epithelial barrier function, as assessed by transepithelial electrical resistance measurement and paracellular permeability assay. Isovalerate upregulated the expression of genes involved in innate immunity, markers of absorptive and enteroendocrine cells, while reducing the expression of stem cells and mucus-related genes. Most of the effects of isovalerate on epithelial cells were also observed with butyrate, an inhibitor of the epigenetic enzymes histone deacetylases (HDAC). We found that isovalerate also inhibited HDAC, although to a lesser extent than butyrate. Furthermore, the structurally unrelated HDAC inhibitor trichostatin A improved epithelial barrier function and upregulated SLPI and IL10RA gene expression, as observed with isovalerate and butyrate. Interestingly, the other two BCFAs, isobutyrate and 2-methylbutyrate, did not replicate the effects of isovalerate. Overall, our in vitro results suggest that targeting the bacterial production of isovalerate may be useful to promote gut health. In this perspective, we performed an in silico analysis that identified species belonging to dominant gut microbiota genera, such as <i>Prevotella, Blautia, Christensenella, Clostridium,</i> and <i>Ruminococcus</i>, as potential producers of BCFAs through the POR enzymatic pathway.<b>NEW & NOTEWORTHY</b> The microbiota degrades branched-chain amino acids to produce branched-chain fatty acids, the effects of which on the intestinal epithelial barrier remain poorly described. In this study, we demonstrate that the leucine-derived metabolite isovalerate enhances epithelial barrier function in cell monolayers derived from porcine ileum organoids. We also identified gut microbiota species potentially able to produce branched-chain fatty acids that could be targeted to promote gut health.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G459-G477"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147289210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Berndt et al., volume 303, 2011, p. G1384-G1392.","authors":"","doi":"10.1152/ajpgi.00095.2026_COR","DOIUrl":"https://doi.org/10.1152/ajpgi.00095.2026_COR","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"330 4","pages":"G495-G497"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoxia-induced fatty liver injury through the AKT-dependent and HIF-2α-independent pathways.","authors":"Youngmi Song, Sung Ryol Lee, Byung-Wan Lee","doi":"10.1152/ajpgi.00334.2025","DOIUrl":"10.1152/ajpgi.00334.2025","url":null,"abstract":"<p><p>Supplemental oxygen is widely used to treat hypoxemia, but prolonged exposure induces oxidative stress. We investigated whether hyperoxia-induced reactive oxygen species contribute to fatty liver injury and delineated the underlying mechanism. To enhance translational relevance, mice were housed under normoxic (21% O₂) or hyperoxic (30% O₂) conditions for 10 days. We also used H₂O₂-treated HepG2 cells and human liver organoids. Western blotting, real-time PCR, and immunostaining were performed to assess molecular changes. Hyperoxia increased systemic oxidative stress, inflammatory markers, liver weights, and hepatic triglyceride (TG) accumulation. These changes were accompanied by repression of fatty acid β-oxidation (FAO) and mitochondrial biogenesis genes and activation of lipogenesis. Hyperoxia also increased glycolysis, as shown by increased glucose transporter 2 (GLUT2) and glucokinase (<i>Gck</i>) expression, and activated protein kinase B (AKT) signaling without altering hypoxia-inducible factor-2α (HIF-2α) expression. Consistently, H₂O₂-treated HepG2 cells and human liver organoids exhibited similar alterations, including TG accumulation, upregulation of glycolytic and lipogenic markers, downregulation of FAO genes, and increased fibrosis marker and inflammation. Notably, si<i>HIF-2α</i> failed to attenuate TG accumulation, confirming an HIF-2α-independent mechanism. Finally, inhibition of AKT signaling attenuated TG accumulation and fibrosis in vitro by preventing glycolysis (via downregulation of <i>GCK</i>) and de novo lipid synthesis, whereas improving mitochondrial function; however, GLUT2 expression remained unaffected. In summary, hyperoxia-induced oxidative stress promotes hepatic TG accumulation and fibrosis by impairing mitochondrial function and enhancing glycolysis and lipogenesis in an AKT-dependent, HIF-2α-independent manner. These findings highlight risks of oxygen therapy on hepatic metabolism and identify AKT signaling as a therapeutic target to mitigate hyperoxia-induced fatty liver injury.<b>NEW & NOTEWORTHY</b> Hyperoxia-induced oxidative stress caused hepatic triglyceride accumulation and fibrosis through mitochondrial dysfunction, suppressed FAO, and enhanced glycolysis and lipogenesis. These effects were AKT-dependent but HIF-2α-independent, highlighting AKT signaling as a potential therapeutic target to mitigate oxygen-related fatty liver injury.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G498-G511"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tools and advanced imaging technologies for assessing intestinal epithelial barrier integrity: a systematic review.","authors":"Sophie Vieujean, Raja Atreya, Andrea Buda, Josselin Caradec, Sandra Citi, Silvio Danese, Olivier Dewit, Matthias Friedrich, Subrata Ghosh, Marietta Iacucci, Vipul Jairath, Arthur Kaser, Rupert W Leong, Markus F Neurath, Nicolas Pierre, Mathilde Pohin, Timo Rath, Pauline Rivière, Simon Travis, James Westcott, Sebastian Zeissig, Laurent Peyrin-Biroulet","doi":"10.1152/ajpgi.00447.2025","DOIUrl":"10.1152/ajpgi.00447.2025","url":null,"abstract":"<p><p>The intestinal epithelium is a key component of the intestinal barrier, which is the largest and most complex barrier of the human body, regulating nutrient absorption while restricting the entry of harmful antigens. Breakdown of this barrier facilitates microbial and dietary antigenic translocation, triggering local immune system activation and inflammation. Although barrier alteration alone may not be sufficient to initiate disease, accumulating evidence highlights its critical role in the pathogenesis and progression of a wide range of gastrointestinal and systemic disorders. Early identification of intestinal epithelium and barrier alterations could enable timely therapeutic approaches. This systematic review provides an overview of current in vivo (both noninvasive and invasive) and ex vivo/in vitro approaches used to assess intestinal epithelial barrier alterations. Noninvasive in vivo approaches rely mainly on urinary detection of orally ingested probes, but their clinical utility is limited by lack of standardization and specificity. Circulating and fecal constitutive markers derived from the intestinal barrier, which reflect epithelial alterations, together with indicators of microbial translocation, provide complementary insights but remain insufficiently validated. Advanced invasive endoscopic modalities such as confocal laser endomicroscopy enable near-histological, real-time visualization but are costly and largely used as research tools in specialist centers. In vitro, transepithelial electrical resistance assessment remains the reference standard, though novel technologies (including impedance spectroscopy and organic electrochemical transistors) offer enhanced sensitivity and resolution. Despite progress, major gaps remain, including the absence of a standardized definition of epithelial barrier breakdown, the lack of a practical diagnostic tool, methodological heterogeneity, unvalidated thresholds, and limited prospective validation.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G424-G458"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma linoleic acid is related to lower hepatic steatosis index and higher linoleate-rich cardiolipin in adults with MAFLD.","authors":"Ali Kalhori, Rachel M Cole, Stephan Zarich, Na Li, Arunark Kolipaka, Ai Ni, Genevieve C Sparagna, Martha A Belury","doi":"10.1152/ajpgi.00344.2025","DOIUrl":"10.1152/ajpgi.00344.2025","url":null,"abstract":"<p><p>Linoleic acid (LA, C18:2n-6) is a required nutrient that supports mitochondrial function as a component of the inner mitochondrial membrane, cardiolipin (CL). Tetralinoleoyl CL (LA₄CL) supports optimal fatty acid oxidation, which is impaired in the liver in adults with metabolic dysfunction-associated fatty liver disease (MAFLD). Data were analyzed from 74 adults with MAFLD recruited from the Columbus region, Ohio, United States. Fatty acid content and CL species were measured in blood and peripheral blood mononuclear cells (PBMCs). Liver fat was assessed using magnetic resonance imaging-proton density fat fraction, and liver stiffness was assessed using magnetic resonance elastography. Although plasma LA was not significantly associated with liver fat or stiffness, there was a borderline inverse association with liver fat in females (<i>P</i> = 0.091). Plasma LA was negatively associated with hepatic steatosis index (<i>P</i> = 0.014) and homeostatic model assessment for insulin resistance (HOMA-IR) (<i>P</i> = 0.05). Plasma LA was positively correlated with LA₄CL in PBMC expressed as a percentage of total cardiolipin (<i>r</i> = 0.501, <i>P</i> < 0.001) and 72-C CL (<i>r</i> = 0.535, <i>P</i> < 0.001). Borderline inverse relationships with liver fat were observed for LA₄CL expressed as a percentage of 72-C CL (<i>P</i> = 0.074) and total CL (<i>P</i> = 0.063). LA₄CL (% of 72-C CL) was positively associated with HOMA-IR in men (<i>P</i> = 0.006) but not women. Plasma LA was inversely associated with the presence of type 2 diabetes mellitus (odds ratio = 0.831, 95% confidence interval = 0.711, 0.955, <i>P</i> = 0.013). Mediation analysis indicated that HOMA-IR accounted for ∼25.2% of this relationship.<b>NEW & NOTEWORTHY</b> Remodeling of cardiolipin (CL) is altered in the peripheral blood mononuclear cells (PBMCs) of individuals with metabolic dysfunction-associated fatty liver disease (MAFLD), with reduced linoleic acid (LA). Whether specific CL species, such as LA₄CL in PBMCs, or circulating LA levels relate to liver stiffness or hepatic fat is unknown. This study identifies both global- and sex-specific associations between plasma LA, PBMC-derived LA₄CL, hepatic fat, liver stiffness, and type 2 diabetes mellitus in adults with MAFLD.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G478-G486"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Esophageal mucosal mast cell density and degranulation are increased in gastroesophageal reflux disease.","authors":"Tom Leech, Madusha Peiris","doi":"10.1152/ajpgi.00402.2025","DOIUrl":"10.1152/ajpgi.00402.2025","url":null,"abstract":"<p><p>Gastroesophageal reflux disease (GERD) is a chronic condition encompassing visceral pain-experienced as heartburn and, in some cases, inflammation of the esophageal mucosa. Although mast cell dysregulation has been described in disorders of gut-brain interaction, it has been understudied in GERD. We aimed to characterize mast cell localization and degranulation in GERD esophageal mucosa. Distal esophageal biopsies were collected from healthy control subjects (HC; <i>n</i> = 10) and subjects with functional heartburn (FH; <i>n</i> = 9), nonerosive reflux disease (NERD; <i>n</i> = 13), and erosive reflux disease (ERD; <i>n</i> = 12). Immunohistochemistry was used to visualize tryptase expression in the esophageal mucosa. The localization of tryptase+ mast cells was identified as intraepithelial or papillary, and the degranulation state of individual mast cells was determined based on the tryptase staining pattern. There was an increased density of mast cells in the esophageal papillae and epithelium of patients with ERD compared with HCs. The density of degranulated intraepithelial mast cells was significantly higher in subjects with FH and subjects with ERD compared with HCs, with a trend toward an increase in NERD. In NERD and ERD, the density of degranulated mast cells in papillae was significantly higher than in HCs. In FH, the density of intraepithelial mast cells positively correlated with reflux disease questionnaire (RDQ) score. Mast cells are more numerous in the esophageal mucosa of subjects with ERD, and activity is increased in subjects with FH, NERD, and ERD. This could contribute to mucosal inflammation, barrier dysfunction, and visceral hypersensitivity in patients with GERD. Future studies should investigate the role of mucosal mast cells in GERD, representing a possible future treatment target.<b>NEW & NOTEWORTHY</b> This is the first study to characterize mast cell localization and degranulation in subjects with pH-phenotyped FH, NERD, and ERD compared with healthy controls, showing elevated mast cell numbers in ERD, with increased degranulation in all patient groups (FH, NERD, and ERD). These findings suggest that mast cell activation may contribute to mucosal inflammation and symptom generation in GERD, particularly FH.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G414-G423"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From rodents to chips: preclinical models of inflammatory bowel disease with emphasis on host-microbiome interactions.","authors":"Satish Kumar, Biswatrish Sarkar","doi":"10.1152/ajpgi.00345.2025","DOIUrl":"10.1152/ajpgi.00345.2025","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic relapsing inflammatory disorder with steadily increasing global prevalence, significantly impairing patient quality of life. Preclinical research in IBD has traditionally relied on animal models to investigate disease etiology, immunopathogenesis, and therapeutic responses. A wide range of experimental models primarily rodents, along with limited use of larger animals such as pigs and nonhuman primates, have been developed to reproduce key clinical, histological, and immunological features of human IBD. These models have played a crucial role in evaluating pharmacological agents, biologics, probiotics, dietary interventions, gene-based therapies, and microbiome-targeted strategies. Notably, accumulating evidence highlights the pivotal role of gut microbiota dysbiosis in disease initiation, progression, and therapeutic responsiveness, making host-microbiome interactions a central component of contemporary IBD research. However, despite their utility, animal models exhibit important limitations related to interspecies differences, incomplete microbiome representation, and poor translational predictability. In response, increasing regulatory pressure from agencies such as the National Institutes of Health (NIH) and FDA to reduce animal experimentation has accelerated the development of human-relevant, nonanimal platforms, including intestinal organoids, in vitro coculture systems, and gut-on-chip technologies. This review critically evaluates existing in vivo IBD models with particular emphasis on their ability to capture immune-microbiome epithelial interactions while also discussing emerging human-derived systems as complementary translational tools. Collectively, the integration of microbiome-responsive and immune-competent-advanced in vitro models represents a promising direction to bridge the gap between experimental findings and clinical application in IBD research.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G397-G413"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MrgprC11 expression and function in vagal afferent nerves in the esophagus.","authors":"Xiaoyun Yu, Yongming Huang, Mayur J Patil, Yanyan Xing, Fei Ru, Ryo Kawamoto, Liang Han, Bradley J Undem, Xinzhong Dong, Shaoyong Yu","doi":"10.1152/ajpgi.00363.2025","DOIUrl":"10.1152/ajpgi.00363.2025","url":null,"abstract":"<p><p>Noxious stimulation-induced esophageal nociception plays a crucial role in generating esophageal pain and heartburn, but the underlying mechanism remains unclear. MrgprC11 is a recently discovered member belonging to Mas1-related G protein-coupled receptor (Mrgpr) family, which is selectively expressed in afferent DRG neurons and distinctively encodes somatic pain and itch sensations. Whether MrgprC11 is also functionally expressed in esophageal afferent neurons and mediates esophageal nociception has yet to be defined. We first compared MrgprC11 mRNA expressions in the esophagus, DRG, and vagal ganglia by RT-PCR. MrgprC11-positive nerve fiber distributions were revealed by confocal imaging in the whole mount esophageal tissues using the MrgprC11^tdTomato mouse. We then addressed the MrgprC11 agonist bovine adrenal medulla peptide 8-22 (BAM8-22)-evoked functional responses in vagal afferent neurons by two-photon imaging using pirt-GCaMP6 mice and in esophageal vagal C-fibers by extracellular recording from wild-type and <i>Mrgpr-clusterΔ</i>^-/- mice. MrgprC11 mRNA expression was identified in the DRG and vagal ganglia, but not the esophagus. MrgprC11-positive nerve fibers were richly distributed in the wall of the esophagus. MrgprC11 agonist BAM8-22 elicited a significant increase in calcium influx in vagal afferent neurons. When applied to the esophageal vagal C-fiber nerve terminals in extracellular recordings, BAM8-22-evoked action potential discharges in the C-fibers only in wild-type but not in <i>Mrgpr-clusterΔ</i>^-/- mice. Following activation, esophageal distension-induced action potential discharges were significantly enhanced in wild-type but not in knockout animals. The present study demonstrated a functional role of MrgprC11 in mediating activation and sensitization of esophageal vagal afferent C-fibers, revealing a new mechanism and potential target for esophageal nociception.<b>NEW & NOTEWORTHY</b> MrgprC11 belongs to the recently discovered Mrgpr family and plays a crucial role in somatic sensory transduction. Its functional expression in visceral esophageal afferent nerves has yet to be defined. The present study demonstrated a functional role of MrgprC11 in mediating activation and sensitization of esophageal vagal afferent C-fibers, revealing a novel nociceptive sensory transduction mechanism in the esophagus.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G341-G348"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of gastrointestinal PDGFRα⁺ cells leads to loss of postjunctional inhibitory motor responses.","authors":"Sung Jin Hwang, Kenton M Sanders, Sean M Ward","doi":"10.1152/ajpgi.00307.2025","DOIUrl":"10.1152/ajpgi.00307.2025","url":null,"abstract":"<p><p>Fibroblast-like cells (FLCs) exist in the smooth muscle layers of visceral organs, yet in many instances their functional role(s) have not been identified. FLCs express platelet-derived growth factor receptor (PDGFR) α and are a novel class of excitable cells recently described in visceral organs. Crenolanib is a benzamidine quinolone derivative originally developed as an inhibitor of PDGFR to treat certain solid tumors with PDGFRα overexpression mutations. In the present study, we used crenolanib to disrupt PDGFRα expression and signaling in the gastrointestinal (GI) tracts of <i>BALB/c</i> mice. Intraperitoneal injections of crenolanib (100 µg/g body wt) or DMSO control vehicle were given to littermates from postpartum P1 through P15. Crenolanib-injected mice were smaller in size and weight. The gastrointestinal tracts were also shorter and appeared partially distended. qPCR revealed downregulation of key gene transcripts involved in PDGFRα cell signaling including <i>Pdgfra</i>, <i>Kcnn3</i>, and <i>P2ry1</i>. Confocal immunofluorescence demonstrated significant decreases in PDGFRα and SK3 protein expression. c-Kit expression was slightly inhibited, but gastric, intestinal, and colonic pacemaker activity was not affected by crenolanib. Purinergic inhibitory postjunctional motor responses were greatly attenuated in the GI tracts of crenolanib-treated animals compared with vehicle-treated controls in response to electric field-evoked nerve stimulation. These data provide evidence for a functional role of PDGFRα⁺ cells in inhibitory neuroeffector motor responses throughout the gastrointestinal tract.<b>NEW & NOTEWORTHY</b> The physiological roles of newly described PDGFRα⁺ interstitial cells in neurotransmission within the gastrointestinal (GI) tract have predominantly come from studies on isolated cells. Here we used an inhibitor of PDGFRα, crenolanib, to examine the effects of PDGFRα⁺ cells in enteric inhibitory neurotransmission. Crenolanib caused loss of PDGFRα⁺ cells and neurally evoked fast inhibitory junction potentials associated with purine neurotransmission, providing evidence for the function of PDGFRα⁺ cells within intact tissues of the GI tract.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G243-G255"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidation of daily timed-palatable meal-anticipatory activity in the circadian system of mice.","authors":"S K Tahajjul Taufique, Averey Eischeid, Isabel Magaña, David E Ehichioya, Sofia Farah, Yuuki Obata, Shin Yamazaki","doi":"10.1152/ajpgi.00368.2025","DOIUrl":"10.1152/ajpgi.00368.2025","url":null,"abstract":"<p><p>Anticipation of daily recurring changes in the environment is critical for survival. When food access is limited to a few hours during the daytime, nocturnal rodents exhibit food-anticipatory activity, which appears a few hours before scheduled mealtime. The rodents are also known to exhibit anticipatory activity for time-restricted palatable meals under ad libitum access to chow. When 1 h of chocolate chip access was given during the day, mice exhibited robust anticipatory activity. In contrast, despite the peanut butter-fed mice eating two times the calories of peanut butter than the chocolate-fed mice did of chocolate chips, we observed only negligible anticipatory activity for daily 1-h peanut butter administration. In ex vivo explants, the phase of the liver in mice subjected to timed-chocolate chip access was significantly advanced, similarly to that in mice subjected to 4-h restricted feeding during the day. Similar to anticipatory activity, negligible phase changes in the liver were observed in the mice given 1 h of peanut butter access during the day. Therefore, robustness of palatable meal-anticipatory activity and phase advance in the liver are unlikely to be in direct response to increased calorie intake during the day. We measured food-seeking nose-poking behavior during food deprivation following daily 1-h chocolate chip access. Mice expressed anticipatory food seeking around the time that they had previously been given daily chocolate chips. This suggests that the time of chocolate chip access is encoded to the same circadian pacemaker that controls food-anticipatory activity.<b>NEW & NOTEWORTHY</b> Anticipatory activity for daily chocolate chip access is stronger than that for daily peanut butter access. Mice given daily chocolate chip access, but not peanut butter access, exhibited altered circadian organization among peripheral clocks. During food deprivation, mice exhibited anticipatory food-seeking behavior at the time they had previously been given chocolate chip access, suggesting that the time of palatable meals is encoded in the circadian pacemaker controlling food-anticipatory activity.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G270-G279"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}