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

{"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}

{"title":"Regulation of pathologic fibroblast functions in digestive diseases: a role for hypoxia?","authors":"Cian M Ohlendieck, Carlos Matellan, Mario C Manresa","doi":"10.1152/ajpgi.00277.2024","DOIUrl":"10.1152/ajpgi.00277.2024","url":null,"abstract":"<p><p>The recent uncovering of fibroblast heterogeneity has given great insight into the versatility of the stroma. Among other cellular processes, fibroblasts are now thought to contribute to the coordination of immune responses in a range of chronic inflammatory diseases and cancer. Although the pathologic roles of myofibroblasts, inflammatory fibroblasts, and cancer-associated fibroblasts in disease are reasonably well understood, the mechanisms behind their activation remain to be uncovered. In the gastrointestinal (GI) tract, several interleukins and tumor necrosis factor superfamily members have been identified as possible mediators driving the acquisition of inflammatory and fibrotic properties in fibroblasts. In addition to cytokines, other microenvironmental factors such as nutrient and oxygen availability are likely contributors to this process. In this respect, the phenomenon of low cellular oxygen levels known as hypoxia is common in a plethora of GI diseases. Indeed, the cross talk between hypoxia and inflammation is well-documented, with an abundance of studies suggesting that oxygen-sensing enzymes may have regulatory effects on inflammatory signaling pathways such as NF-κB. However, the impact that this has in GI fibroblasts in the context of chronic diseases has not been fully uncovered. Here we discuss the role of fibroblasts in GI diseases, the mediators that have emerged as regulators of their functions and the potential impact of hypoxia in this process, highlighting areas that require further investigation.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G229-G242"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051374","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":"The central neural control of the posterior belly of the digastric muscles during swallowing in rats.","authors":"Yuhei Tsutsui, Titi Chotirungsan, Charng-Rong Pan, Satomi Kawada, Jin Magara, Takanori Tsujimura, Keiichiro Okamoto, Makoto Inoue","doi":"10.1152/ajpgi.00374.2024","DOIUrl":"10.1152/ajpgi.00374.2024","url":null,"abstract":"<p><p>The aim of this study was to clarify whether the posterior belly of the digastric (post-Dig) muscle is activated during the swallowing reflex and whether the post-Dig muscle is directly controlled by the swallowing central pattern generator (CPG) in anesthetized rats, using physiological and immunohistochemical approaches. In physiological study, electromyograms (EMGs) of the post-Dig, sternohyoid and thyrohyoid muscles, and the diaphragm were recorded during respiration and swallowing with and without airway stenosis. In the immunohistochemical study, c-Fos immunoreactivity for expression of cells during swallowing was analyzed. Motoneurons were identified using immunohistochemistry with Fluoro-gold (FG). EMG bursts were observed in the hyoid muscles during the inspiratory phase and swallowing. With airway stenosis, the swallowing EMG activity was facilitated in terms of duration and area only in the post-Dig muscle. The coordination of these EMG activities during swallowing was maintained with airway stenosis. In contrast, the offset of the post-Dig EMG burst was delayed with airway stenosis. c-Fos-positive cells were observed in the accessory facial nucleus (Acs7), but only in the rostral portion. FG-labeled cells were observed in Acs7. Several c-Fos/FG double-labeled cells were observed only in the rostral Acs7. These results suggested that the post-Dig muscle is activated during swallowing, the activation of which is controlled by the swallowing CPG, and that the distribution of Acs7 neurons, which innervate the post-Dig muscle, was uneven in the nucleus. In addition, the modulation of post-Dig muscle activity during inspiration might be due to changes in peripheral conditions via respiratory CPG.<b>NEW & NOTEWORTHY</b> The posterior belly of the digastric muscle is activated during the inspiratory phase and swallowing. Increased airway resistance facilitates both inspiratory and swallowing activities of this muscle. Immunohistochemistry revealed that the motoneurons innervating the posterior belly of the digastric muscle were activated during swallowing only in the rostral portion of the accessory facial nucleus. These results suggested that the posterior belly of the digastric muscle is controlled by the respiratory and swallowing central pattern generators.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G277-G288"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188205","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":"Intestinal organoid coculture systems: current approaches, challenges, and future directions.","authors":"Ghanyah Al-Qadami, Anita Raposo, Chia-Chi Chien, Chenkai Ma, Ilka Priebe, Maryam Hor, Kim Fung","doi":"10.1152/ajpgi.00203.2024","DOIUrl":"10.1152/ajpgi.00203.2024","url":null,"abstract":"<p><p>The intestinal microenvironment represents a complex and dynamic ecosystem, comprising a diverse range of epithelial and nonepithelial cells, a protective mucus layer, and a diverse community of gut microbiota. Understanding the intricate interplay between these components is essential for uncovering the mechanisms underlying intestinal health and disease. The development of intestinal organoids, three-dimensional (3-D) mini-intestines that closely mimic the architecture, cellular diversity, and functionality of the intestine, offers a powerful platform for investigating different aspects of intestinal physiology and pathology. However, current intestinal organoid models, mainly adult stem cell-derived organoids, lack the nonepithelial and microbial components of the intestinal microenvironment. As such, several coculture systems have been developed to coculture intestinal organoids with other intestinal elements including microbes (bacteria and viruses) and immune, stromal, and neural cells. These coculture models allow researchers to recreate the complex intestinal environment and study the intricate cross talk between different components of the intestinal ecosystem under healthy and pathological conditions. Currently, there are several approaches and methodologies to establish intestinal organoid cocultures, and each approach has its own strengths and limitations. This review discusses the existing methods for coculturing intestinal organoids with different intestinal elements, focusing on the methodological approaches, strengths and limitations, and future directions.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G252-G276"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880792","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":"Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.","authors":"Elizabeth C Rose, Jeremy M Simon, Ismael Gomez-Martinez, Scott T Magness, Jack Odle, Anthony T Blikslager, Amanda L Ziegler","doi":"10.1152/ajpgi.00194.2024","DOIUrl":"10.1152/ajpgi.00194.2024","url":null,"abstract":"<p><p>Intestinal ischemic injury damages the epithelial barrier and predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age dependency in intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier compared with older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs, which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells from recovering ischemic jejunum of juvenile pigs underwent single-cell transcriptomics and the predicted upstream regulator, colony stimulating factor-1 (CSF-1), was interrogated in our model. A subcluster of absorptive enterocytes expressed several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation by colony stimulating factor-1 (CSF-1). We validated age-dependent induction of <i>CSF-1</i> by ischemia and documented that CSF-1 and colony-stimulating factor-1 receptor (CSF1R) co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued neonates. Furthermore, the CSF-1 blockade reduced restitution in vitro, and CSF-1 improved barrier function in injured neonatal pigs in preliminary ex vivo experiments. These studies validate an approach to inform potential novel therapeutic targets, such as CSF-1, to improve outcomes in neonates with intestinal injury in a unique pig model.<b>NEW & NOTEWORTHY</b> These studies validate an approach to identify and predict upstream regulation of restituting epithelium in a unique pig intestinal ischemic injury model. Identification of potential molecular mediators of restitution, such as CSF-1, will inform the development of targeted therapeutic interventions for the medical management of patients with ischemia-mediated intestinal injury.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G182-G196"},"PeriodicalIF":3.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031842","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":"Plasticity of enteric neurotransmission varies during day-night cycles and with feeding state.","authors":"Anita J L Leembruggen, Gunes S Yildiz, Justin P Hardee, Lincon A Stamp, Joel C Bornstein, Marlene M Hao","doi":"10.1152/ajpgi.00286.2024","DOIUrl":"10.1152/ajpgi.00286.2024","url":null,"abstract":"<p><p>The circadian cycle is a fundamental biological rhythm that governs many physiological functions across nearly all living organisms. In the gastrointestinal tract, activities such as gut motility, hormone synthesis, and communication between the gut, central nervous system, and microbiome all fluctuate in alignment with the circadian cycle. The enteric nervous system (ENS) is critical for coordinating many of these activities; however, how its activity is governed by the circadian cycle remains unknown. In this study, we used live calcium imaging to examine alterations in enteric neurotransmission during the 24-h day/night cycle in mice. In addition, given the role of food timing as a potent circadian entrainer, we also investigated the impact of an acute 13-h fast on ENS activity. Our findings reveal that enteric neuronal activity typically increases during the dark phase but shifts to the light phase following an acute fast. Importantly, these changes in neuronal activity were not accompanied by alterations in the gene expression of associated neurotransmitter receptors.<b>NEW & NOTEWORTHY</b> Neuronal activity in the enteric nervous system changes during the 24-h day/night cycle, with increased neuronal function detected at night when mice are feeding and active. However, following an acute fast, neuronal sensitivity becomes more pronounced during the day. These changes in neuronal function did not correlate with changes in neurotransmitter receptor gene expression levels.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"328 2","pages":"G145-G151"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055762","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":"Local tissue response to a C-X-C motif chemokine ligand 12 therapy for fecal incontinence in a rabbit model.","authors":"Hannah M Ruetten, Shannon S Lankford, Abolfazl S Abdolmaleki, Nicholas Edenhoffer, Gopal Badlani, James K Williams","doi":"10.1152/ajpgi.00343.2024","DOIUrl":"10.1152/ajpgi.00343.2024","url":null,"abstract":"<p><p>This study aimed to determine if local injection of C-X-C motif chemokine ligand 12 (CXCL12) reduces sphincter fibrosis, restores sphincter muscle content, vascularization, and innervation, and recruits progenitor cells in a rabbit model of anal sphincter injury and incontinence. Adult female rabbits were assigned to three groups: uninjured/no treatment (control), injured/treated (treated), and injured/no treatment (untreated) (<i>n</i> = 4 each). Injured groups were anesthetized, and a section of external anal sphincter was removed at the 9 o'clock position. The treated sphincters were injected with 200 ng of human recombinant CXCL12 6 wk after injury, and necropsy was performed 6-wk post-treatment. The external anal sphincter was removed, fixed, embedded in paraffin, sectioned, and mounted to slides for histologic analysis of collagen and muscle content and fiber characteristics: innervation, vascularization, and progenitor cell content. Compared with controls, untreated had significantly decreased total skeletal muscle, indistinct muscle layers, and disorganized circumferential and inner longitudinal layers at the injury site. Untreated also had significantly increased collagen fiber density at the injury site compared with treated and controls. Cells staining positive for CD34 within the skeletal muscle layer were increased in treated and untreated compared with controls. Staining density for markers of nerves and vascular endothelium, cells staining positive for CD34 within the mucosa/submucosae, and cells staining positive for PAX7 were similar among all groups. Local injection of CXCL12 reduces postinjury fibrosis and results in statistically similar muscle content and organization between treated animals and controls. Further studies are needed for this promising new treatment for postparturient anal sphincter injury.<b>NEW & NOTEWORTHY</b> Local injection of CXCL12 cytokine reduces postinjury fibrosis in a rabbit model of anal sphincter injury and fecal incontinence. The larger size of the rabbits aided in targeted injury and treatment. Further studies are needed to explore noninvasive treatment options for postparturient anal sphincter injury.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G136-G144"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913733","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":"Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rats.","authors":"Qian Wu, Jing Wang, Chuyue Tu, Peiru Chen, Yahui Deng, Lixiu Yu, Xiaojin Xu, Xiangming Fang, Weiyong Li","doi":"10.1152/ajpgi.00167.2024","DOIUrl":"10.1152/ajpgi.00167.2024","url":null,"abstract":"<p><p>Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the cross talk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.<b>NEW & NOTEWORTHY</b> Patients who were less inclined to have olanzapine-induced fatty liver had different gut microbiota profiles than did those in the susceptible cohort. Lachnospiraceae, Ruminococcaceae, Oscillospiraceae, Butyricicoccaceae, and Christensenellaceae were enriched in patients who were less prone to fatty liver disease caused by olanzapine. Fecal microbiota treatment (FMT) with these fecal samples promoted short-chain fatty acid (SCFA) production, which attenuated the circulating leptin and inhibited FASN and ACC1, thereby suppressing lipid synthesis in the liver, ultimately leading to alleviation of hepatic steatosis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G110-G124"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827059","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":"Bile acid sequestrant inhibits gluconeogenesis via inducing hepatic cysteine dioxygenase type 1 to reduce cysteine availability.","authors":"David J Matye, Huaiwen Wang, Yifeng Wang, Lei Xiong, Tiangang Li","doi":"10.1152/ajpgi.00353.2024","DOIUrl":"10.1152/ajpgi.00353.2024","url":null,"abstract":"<p><p>Bile acid sequestrants such as cholestyramine (ChTM) are gut-restricted bile acid-binding resins that block intestine bile acid absorption and attenuate hepatic bile acid signaling. Bile acid sequestrants induce hepatic bile acid synthesis to promote cholesterol catabolism and are cholesterol-lowering drugs. Bile acid sequestrants also reduce blood glucose in clinical trials and are approved drugs for treating hyperglycemia in type-2 diabetes. However, the mechanisms mediating the glucose-lowering effect of bile acid sequestrants are still incompletely understood. Here we showed that ChTM treatment decreased hepatic glucose production in Western diet-fed mice with paradoxically induced hepatic gluconeogenic genes. Cysteine dioxygenase type 1 (CDO1) mediates cysteine conversion to taurine and its expression is repressed by bile acids. We show that ChTM induced hepatic CDO1 and selectively reduced hepatic cysteine availability. Knockdown of liver CDO1 increased liver cysteine and glucose production in mice, whereas hepatocytes cultured in cystine-deficient medium showed reduced glucose production. By using dietary protein-restricted and cystine-modified Western diets that selectively alter hepatic cysteine availability, we found that reduced hepatic cysteine availability strongly inhibited glucose production in mice. Interestingly, chronic dietary protein restriction also prevented Western diet-induced obesity, which was fully reversed by restoring dietary cystine intake alone. Consistently, reduced cysteine availability dose-dependently inhibited adipogenesis in vitro. In conclusion, we report that the glucose-lowering effect of bile acid sequestrants is mediated by a CDO1-induced hepatic cysteine restriction mimetic effect. Furthermore, the anti-obesity effect of dietary protein restriction is largely mediated by reduced dietary cysteine intake.<b>NEW & NOTEWORTHY</b> Hepatic cysteine availability is a key driver of hepatic gluconeogenesis. Bile acid sequestrant inhibits gluconeogenesis by inducing CDO1-mediated cysteine catabolism to reduce cysteine availability. Dietary protein restriction causes hepatic cysteine deficiency without overall amino acid deficiency. The glucose-lowering effect of dietary protein restriction is largely mediated by lower dietary cysteine intake. The anti-obesity effect of chronic dietary protein restriction is largely mediated by lower dietary cysteine intake.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G166-G178"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998521","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":"Deleterious impacts of Western diet on jejunum function and health are reversible.","authors":"Sarah Carpinelli, John Ahlert, Maxwell Rubin, Alex Aratani, Emma Smith, Dana Floyd, Ross M Potter, Layla Al-Nakkash","doi":"10.1152/ajpgi.00160.2024","DOIUrl":"10.1152/ajpgi.00160.2024","url":null,"abstract":"<p><p>The goal of this study was to determine whether the influence of a high-fat high-sugar diet (Western diet) on intestinal function and health was reversible. We measured transepithelial short circuit current (<i>I</i>_sc), across freshly isolated segments of jejunum from male C57Bl/6J mice randomly assigned to one of the following groups for the study duration: high-fat high-sugar diet for 24 wk (HFHS), HFHS diet for 12 wk then switched to standard chow and water for a further 12 wk (Std), and lean controls (standard chow and water for 24 wk). At the completion of the study, segments of jejunum were frozen for Western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum and tissue assays were performed. Basal <i>I</i>_sc was significantly decreased (by 42%, <i>P</i> < 0.05) in HFHS versus leans. This decrease in <i>I</i>_sc was fully reversed by switching to Std diet. The HFHS-induced decrease in <i>I</i>_sc was attributed to a significant loss of calcium-activated chloride channel (ClC2) expression. Changes in inflammatory state (TNF-α) and intestinal health [myeloperoxidase (MPO) activity] were associated with body weight changes. Our data suggests that the reduced basal jejunal <i>I</i>_sc in HFHS mice is reversible. Better understanding of Western diet-mediated intestinal disturbances may permit for improved treatment options for gastrointestinal abnormalities in obese individuals.<b>NEW & NOTEWORTHY</b> Our data suggests that the reduced basal jejunal <i>I</i>_sc (decreased secretory function) in Western diet-fed mice is reversible. A better understanding of Western diet-mediated intestinal disturbances may permit improved treatment options for gastrointestinal abnormalities in obese individuals.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G83-G93"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875576","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}