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

{"title":"DIFFERENTIAL RESPONSES TO PROSTAGLANDINS IN THE CIRCULAR AND LONGITUDINAL MUSCLE LAYERS OF THE MURINE ILEUM.","authors":"Joong Goo Kwon, Sung Jin Hwang, Elizabeth A H Beckett, Kenton M Sanders, Sean Ward","doi":"10.1152/ajpgi.00400.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00400.2024","url":null,"abstract":"<p><p>Prostaglandin E₂ (PGE₂) actions on intestinal motility are complex due the differential expression of the PGE₂ receptors EP1-EP4. We sought to determine the actions of PGE₂ on electrical pacemaker and contractile activity of the circular and longitudinal muscle layers of the murine small intestine. Intracellular microelectrode and isometric force measurements were performed to examine the effects of PGE₂ receptor activation on circular and longitudinal muscle layers. In the two muscle layers PGE₂ produced differential responses. In the circular muscle layer PGE₂ caused dose-dependent membrane hyperpolarization and reduction in slow wave amplitude, accompanied by a decrease in the amplitude of phasic contractions. Membrane hyperpolarization and the reduction in slow wave amplitude and phasic contractions were insensitive to TTX and L-NNA, but inhibited by the K_ATP channel antagonist, glibenclamide. The actions of PGE₂ on the circular muscle layer were mimicked by the selective EP₂ and EP₄ agonists ONO AE1-259 and ONO AE1-329, respectively. The actions of PGE₂ were partially inhibited by the EP4 antagonist ONO AE3-208. The EP₁ agonist ONO DI-004 produced little effect while the EP3 agonist ONO AE-248 caused dose-dependent membrane depolarization. In comparison, PGE₂ produced increased tone and phasic contractions in the longitudinal muscle layer that was mimicked by ONO DI-004 and ONO AE-248, while EP₂ and EP₄ agonists had little effect on contractile activity. These data suggest that differential expression of PGE₂ receptors on intestinal muscle layers can produce antagonistic actions on intestinal motility.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565583","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":"Dynamics of circulatory monocytes trafficking and transitioning to gastric resident macrophages in diabetic gastroparesis.","authors":"Rajan Singh","doi":"10.1152/ajpgi.00053.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00053.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539965","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":"Combination of dietary fiber and exercise training improves fat loss in mice, but does not ameliorate MASLD more than exercise alone.","authors":"Artemiy Kovynev, Mikołaj M Charchuta, Amina Begtašević, Quinten R Ducarmon, Patrick C N Rensen, Milena Schönke","doi":"10.1152/ajpgi.00317.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00317.2024","url":null,"abstract":"<p><p><b>Background:</b> Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. <b>Methods:</b> Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. <b>Results:</b> Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss, and decreased plasma triglyceride and cholesterol levels compared to sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera <i>Anaerostipes</i> and <i>Muribaculaceae</i>, while, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. <b>Conclusion:</b> Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis, but does not have an additional synergistic positive effect on liver health compared to exercise training alone.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539852","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":"Diet-microbiome-ENS connection: impact of the cafeteria diet.","authors":"Arun Balasubramaniam, Shanthi Srinivasan","doi":"10.1152/ajpgi.00391.2024","DOIUrl":"10.1152/ajpgi.00391.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G179-G181"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051370","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":"Prenatal lipopolysaccharide stimulation modulates gastrointestinal immunity and oxidative status in weaned pigs.","authors":"Ty M Mitchell, Nicole C Burdick Sanchez, Jeff A Carroll, Paul R Broadway, Jerrad F Legako, Brooke M Bowen, Amy L Petry","doi":"10.1152/ajpgi.00268.2024","DOIUrl":"10.1152/ajpgi.00268.2024","url":null,"abstract":"<p><p>Gastrointestinal immunity and antioxidant defenses may be bolstered in young animals through prenatal immune stimulation (PIS), but this is largely uninvestigated in swine. This study tested the hypothesis that PIS could regulate offspring's gastrointestinal immune response and oxidative stress profile. To this end, a PIS model was utilized in sows, delivering low-dose lipopolysaccharide (LPS) during the final third of gestation to target the developing immune system. On day 78 ± 1.8 of gestation, 14 Camborough sows (parity = 2.6 ± 1.4) received either saline (Control, CON) or LPS from <i>Escherichia coli</i> O111:B4 (2.5 µg/kg of body wt). A subset of 34 weaned barrows (<i>n</i> = 17 CON, PIS), weaned at 21 ± 1.3 days, were anesthetized for subcutaneous temperature loggers and jugular catheter placement. Following recovery, all pigs received an intravenous injection of LPS (10 µg/kg·body wt) from <i>E. coli</i> O111:B4. Our findings demonstrate that PIS enhances the gut immune response by upregulating key inflammatory cytokines, indicative of a proinflammatory profile. Consistently across the jejunum and ileum, stem cell factor was modulated with heightened expression in PIS than CON (<i>P</i> ≤ 0.05). In the ileum alone, PIS exhibited heightened expression of proinflammatory cytokines and chemokines, including TNFα, IL-6, IL-1β, and CCL3L1, compared with CON (<i>P</i> ≤ 0.05). Exposure to PIS resulted in reduced systemic total antioxidant capacity at <i>hours 2</i> and <i>4</i> postchallenge (<i>P</i> = 0.004). Piglets exposed to PIS had decreased jejunal tissue malondialdehyde concentrations (<i>P</i> = 0.049). Together, these data indicate that exposure to PIS alters the inflammatory profile of the gastrointestinal immune response and oxidative status in weaned pigs.<b>NEW & NOTEWORTHY</b> These studies represent novel investigations into the influence of prenatal immune stimulation (PIS) in swine on the gastrointestinal immune response and oxidative status of offspring following subsequent immune challenge. Notable alterations were observed in gut protein biomarkers, particularly the upregulation of proinflammatory cytokines TNFα, IL-6, and IL-1β in PIS-exposed pigs, but has variable effects on oxidative status. Altered intestinal immune development may contribute to an increased risk for inflammatory disease associated with prenatal immune stimulation.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G197-G205"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031841","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":"A menu for microbes: unraveling appetite regulation and weight dynamics through the microbiota-brain connection across the lifespan.","authors":"Gabriela Ribeiro, Harriët Schellekens, Cristina Cuesta-Marti, Ivie Maneschy, Shámila Ismael, Amanda Cuevas-Sierra, J Alfredo Martínez, Marta P Silvestre, Cláudia Marques, André Moreira-Rosário, Ana Faria, Luis A Moreno, Conceição Calhau","doi":"10.1152/ajpgi.00227.2024","DOIUrl":"10.1152/ajpgi.00227.2024","url":null,"abstract":"<p><p>Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut-microbiota-targeted approaches such as pre-, pro-, post-, and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is <i>1</i>) to provide an overview of the role of the microbiota-gut-brain axis in appetite regulation across the lifespan and <i>2</i>) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G206-G228"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982495","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":"Carbon monoxide produced by HO-1 upregulation is the main factor behind the abnormal motility seen in experimental ulcerative colitis in mice.","authors":"Mengchao Zhao, Yaru Lei, Mengyuan Wang, Yixin Chen, Shaozhang Hou, Xinyuan Dai, Di Gao, Yudan Liu, Bruno Mazet, Lei Sha","doi":"10.1152/ajpgi.00179.2023","DOIUrl":"10.1152/ajpgi.00179.2023","url":null,"abstract":"<p><p>The colonic motility is altered in patients with ulcerative colitis (UC), but the mechanism is not clear. Carbon monoxide (CO) is the molecule regulating the resting membrane potential (RMP) gradient across colonic smooth muscle wall. Changes in RMP will affect the contractility of smooth muscle. In this study, we investigated the altered colonic motility in dextran sodium sulfate-induced UC mice and the role of CO. The results showed that in the UC group, the frequency of spontaneous colonic contractions was increased while the AUC was decreased compared with the control group. HO-1-, but not HO-2-, positive cells were increased in the colonic smooth muscle wall of the UC group. These HO-1-positive cells were mainly in the myenteric plexus and PGP9.5 positive, suggesting neuronal overproduction of CO. The RMP of circular smooth muscle cells (SMCs) in the colon of UC group was hyperpolarized compared with that of control group. In control group, application of CORM-3, a CO donor, altered colonic spontaneous contractions by increasing their frequency and decreasing amplitude. In the UC group, ZnPPIX, a HO-1 inhibitor, reduced the frequency and increased the amplitude. CORM-3 hyperpolarized the RMP of colonic SMCs and abolished its gradient in the control group, while ZnPPIX depolarized the RMP of colonic SMCs and restored its gradient in the UC group. CO produced by HO-1 upregulation is the main factor behind the altered colonic motility seen in UC mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.<b>NEW & NOTEWORTHY</b> Carbon monoxide (CO) produced by HO-1 upregulation in myenteric plexus is the main factor that abolishes the RMP gradient across colonic muscle wall causing the altered colonic motility seen in experimental ulcerative colitis (UC) mice. CO is a potential candidate as a therapeutic target for patients with UC who suffer from abnormal colonic motility.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G311-G322"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381562","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":"Dysregulated hepatic alcohol metabolism: a key factor involved in the pathogenesis of alcohol-associated liver disease.","authors":"Mukund Srinivasan, Sumedha Kota, Kamlesh Bhopale, Anna Caracheo, Lata Kaphalia, Jennifer Linares, Trevor Romsdahl, William Russell, Vsevolod Popov, Paul Boor, Bhupendra Kaphalia","doi":"10.1152/ajpgi.00394.2024","DOIUrl":"10.1152/ajpgi.00394.2024","url":null,"abstract":"<p><p>Alcohol use disorder is a major risk factor for alcohol-associated liver disease (ALD), characterized by reduced hepatic alcohol dehydrogenase (ADH) activity, increased body burden of alcohol, and its nonoxidative metabolism to fatty acid ethyl esters (FAEEs). However, the mechanism(s) underlying ALD remain unclear. This study investigated the metabolic basis and mechanism(s) of ALD in chronic ethanol (EtOH)-fed hepatic ADH1-deficient (ADH^-) deer mice administered with a single dose of binge EtOH with/without FAEEs. Hepatic ADH^- and ADH normal (ADH⁺) deer mice fed chronic EtOH daily for 3 mo, followed by a single dose of binge EtOH (3 g/kg·body wt) with/without FAEEs (100 mg/kg·body wt), 1 wk before euthanasia. Blood alcohol and acetaldehyde and liver injury markers in the plasma, hepatic FAEEs, lipids, and inflammatory markers were analyzed. Hepatic histology, ultrastructure, protein/mRNA expression of genes involved in alcohol metabolism and lipogenesis, cyclic adenosine monophosphate (cAMP), phosphodiesterase (PDE) activity, and AMP-activated protein kinase (AMPKα) signaling were assessed. Blood alcohol, hepatic lipids and FAEEs, inflammation, oxidative stress, and the expression of lipogenic proteins/genes were significantly increased in various chronic EtOH-fed groups of ADH^- versus ADH⁺ deer mice. In addition, hepatic cAMP levels were reduced, whereas PDE activity and plasma transaminases were elevated. Binge EtOH with/without FAEEs did not significantly exacerbate the liver injury in chronic EtOH-fed ADH^- as well as ADH⁺ deer mice. Overall, an increased body burden of EtOH and endogenously formed FAEEs due to hepatic ADH deficiency, along with dysregulated cAMP and AMPKα signaling, could be the determining factors for EtOH-induced liver injury leading to ALD.<b>NEW & NOTEWORTHY</b> Using hepatic alcohol dehydrogenase deficient (ADH^-) deer mouse, which mimics the metabolic conditions observed in chronic alcoholics, we found significant hepatic injury along with degenerative changes in endoplasmic reticulum and mitochondria. Our findings suggest that an increased nonoxidative alcohol metabolism under hepatic alcohol dehydrogenase deficiency and associated hepatic lipid dysregulation and injury appear to be the key factors involved in the pathogenesis of alcohol-associated liver disease.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G289-G308"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188204","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":"Modeling the kinetics of interorgan arginine metabolism during bacterial sepsis in swine.","authors":"Caitlin Vonderohe, Douglas Burrin","doi":"10.1152/ajpgi.00375.2024","DOIUrl":"10.1152/ajpgi.00375.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G309-G310"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063132","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":"Voltage-gated calcium channel α₂δ-1 subunit is involved in the regulation of glucose-stimulated GLP-1 secretion in mice.","authors":"Yuhan Yang, Shunsuke Yamane, Norio Harada, Eri Ikeguchi-Ogura, Kana Yamamoto, Naoki Wada, Muhammad Fauzi, Takaaki Murakami, Daisuke Yabe, Yoshitaka Hayashi, Nobuya Inagaki","doi":"10.1152/ajpgi.00279.2024","DOIUrl":"10.1152/ajpgi.00279.2024","url":null,"abstract":"<p><p>Glucagon-like peptide-1 (GLP-1) is an incretin produced by enteroendocrine preproglucagon (PPG)-expressing cells in response to nutrient ingestion that potentiates insulin secretion. The voltage-gated Ca²⁺ channel has been reported previously to be involved in glucose-stimulated GLP-1 secretion; in this study, we show that PPG-cells in upper and lower small intestine substantially express the voltage-gated Ca²⁺ channel α₂δ-1 subunit (Ca_Vα₂δ-1). In vitro experiments using NCI-H716 cells demonstrate that inhibition of Ca_Vα₂δ-1 by gabapentin (GBP), an inhibitory ligand of the α₂δ subunit, attenuates glucose-stimulated intracellular calcium elevation and reduces GLP-1 secretion. In addition, systemic administration of gabapentin significantly reduces glucose-stimulated GLP-1 secretion without affecting blood glucose levels in wild-type mice. Furthermore, knockout mice of intestine-specific <i>Cacna2d1</i>, a gene encoding Ca_Vα₂δ-1, exhibit reduced GLP-1 secretion in response to oral glucose administration regardless of sex. These results demonstrate that Ca_Vα₂δ-1 expressed in PPG-cells plays an important role in glucose-stimulated GLP-1 secretion and represents a potential target in the treatment of diabetes and obesity.<b>NEW & NOTEWORTHY</b> In this study, we establish high expression of the voltage-gated Ca²⁺ channel α₂δ-1 subunit (Ca_Vα₂δ-1) subunit in enteroendocrine glucagon-like peptide-1 (GLP-1) producing cells and elucidate its role in GLP-1 secretion, providing a more detailed understanding of the mechanism of GLP-1 secretion.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G243-G251"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363192","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}