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

筛选
英文 中文
Sex Dimorphism and Substrate Dependency of Liver Mitochondrial Bioenergetics and H2O2 Production. 肝脏线粒体生物能量和H2O2产生的性别二态性和底物依赖性。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-17 DOI: 10.1152/ajpgi.00196.2025
Devanshi D Dave, Pardis Taheri, Sri Rahavi Boovarahan, Joohyun Kim, Allen W Cowley, Said H Audi, Ranjan K Dash
{"title":"Sex Dimorphism and Substrate Dependency of Liver Mitochondrial Bioenergetics and H<sub>2</sub>O<sub>2</sub> Production.","authors":"Devanshi D Dave, Pardis Taheri, Sri Rahavi Boovarahan, Joohyun Kim, Allen W Cowley, Said H Audi, Ranjan K Dash","doi":"10.1152/ajpgi.00196.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00196.2025","url":null,"abstract":"<p><p>Mitochondrial bioenergetics and H<sub>2</sub>O<sub>2</sub> production play a central role in maintaining liver metabolic function and redox balance. Understanding sex dimorphism and substrate dependency in these mitochondrial processes is crucial for elucidating the regulatory mechanisms that govern male vs. female differences in liver physiology in health and disease. This study aimed at investigating sex-specific and substrate-dependent alterations in liver mitochondrial respiratory rates (JO<sub>2</sub>), membrane potential (ΔΨ), and H<sub>2</sub>O<sub>2</sub> production and their metabolic regulation. Liver mitochondria were isolated from adult male and female Sprague-Dawley (SD) rats. Four substrate combinations-pyruvate+malate (PM), glutamate+malate (GM), succinate, and succinate with complex I inhibitor rotenone (SR)-were used to determine their impact on the activities of the electron transport chain (ETC) and TCA cycle complexes. ADP was added to determine the influence of substrates on oxidative phosphorylation (OxPhos). JO<sub>2</sub> and ΔΨ were measured simultaneously using an Oroboros Oxygraph-2k respirometer with the cationic rhodamine dye TMRM. H<sub>2</sub>O<sub>2</sub> production was measured spectrofluorometrically using the Amplex Red and Horseradish Peroxidase assay. Our results show that male and female liver mitochondria displayed distinct respiratory patterns for different substrates. GM and succinate yielded higher JO<sub>2</sub>, while PM yielded the lowest JO<sub>2</sub>. Notably, female mitochondria exhibited higher JO<sub>2</sub> than males across all substrates. Both ΔΨ and H₂O₂ production showed substrate-dependent patterns, with females exhibiting higher values than males across all substrates. These findings reveal sex-specific differences in liver mitochondrial function, driven by substrate-dependent engagement of the ETC and TCA cycle complexes towards OxPhos, with females showing higher respiratory capacity and H<sub>2</sub>O<sub>2</sub> production.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312196","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}
引用次数: 0
Loss of hepatic alpha-1b adrenoceptor exacerbates inflammation and stellate cell activation in diet-induced MASLD. 在饮食诱导的MASLD中,肝脏α -1b肾上腺素能受体的丧失会加剧炎症和星状细胞活化。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-14 DOI: 10.1152/ajpgi.00143.2025
Bernie Efole, Sarra Beji, Mathilde Mouchiroud, Yves Gélinas, Coraline Canivet, Jocelyn Trottier, Cindy Serdjebi, Joel K Elmquist, Jessica Deslauriers, Olivier Barbier, Alexandre Caron
{"title":"Loss of hepatic alpha-1b adrenoceptor exacerbates inflammation and stellate cell activation in diet-induced MASLD.","authors":"Bernie Efole, Sarra Beji, Mathilde Mouchiroud, Yves Gélinas, Coraline Canivet, Jocelyn Trottier, Cindy Serdjebi, Joel K Elmquist, Jessica Deslauriers, Olivier Barbier, Alexandre Caron","doi":"10.1152/ajpgi.00143.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00143.2025","url":null,"abstract":"<p><p>The brain regulates liver metabolism through neuroendocrine and autonomic pathways, which can be disrupted in metabolic dysfunction-associated steatotic liver disease (MASLD). While autonomic dysfunction, including liver neuropathy, has been reported in MASLD, the role of hepatic sympathetic signaling in disease progression remains unclear. Recent studies show that liver innervation is predominantly of sympathetic nature, suggesting that adrenergic receptors in hepatocytes may influence the pathogenesis of MASLD. We previously identified adrenoceptor alpha-1b (ADRA1B) as the dominant hepatic adrenergic receptor. Here we hypothesized that ADRA1B plays a protective role in MASLD progression. To test this, we generated hepatocyte-specific <i>Adra1b</i> knockout mice (<i>Adra1b</i><sup>LKO</sup>) and induced MASLD with the GAN diet for up to 32 weeks. Liver pathology was quantified by automated image analysis (MorphoQuant), and metabolic phenotyping included glucose tolerance, insulin sensitivity, bile acid composition. Hepatocyte-specific <i>Adra1b</i> deletion did not affect body weight, hepatic lipid accumulation, glucose tolerance, or insulin sensitivity. However, <i>Adra1b</i><sup>LKO</sup> mice exhibited significantly increased hepatic inflammation compared to wild-type controls. These changes were associated with higher hepatic expression of <i>tumor necrosis factor</i> (<i>Tnf</i>) and <i>interleukin-1b</i> (<i>Il1b</i>), as well as an increase in monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). We also observed elevated transforming growth factor beta (TGF-β) and α-smooth muscle actin (<i>Acta2</i>) expression, suggesting activation of hepatic stellate cells. Additionally, <i>Adra1b</i><sup>LKO</sup> mice displayed higher circulating bilirubin levels, with no significant alterations in albumin and bile acid pool composition. These findings reveal a previously unrecognized role for hepatic ADRA1B in restraining inflammatory responses in MASLD. Loss of <i>Adra1b</i> signaling promotes hepatic inflammation, highlighting a neuroimmune mechanism that may be targeted to prevent disease progression.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290573","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}
引用次数: 0
N-glycans on SLC26A3 do not significantly alter plasma membrane or lipid raft trafficking, but appear to stabilize interdomain contacts to stimulate transport. SLC26A3上的n -聚糖不显著改变质膜或脂筏运输,但似乎稳定域间接触以刺激运输。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-10 DOI: 10.1152/ajpgi.00362.2024
Sophie Achilles, Jan-Niklas Tomczak, Fabiane-Samira Baumann, Bassam G Haddad, Stefan Oswald, Jan-Philipp Machtens, Eric R Geertsma, Ilka Wittig, Georg Lamprecht
{"title":"N-glycans on SLC26A3 do not significantly alter plasma membrane or lipid raft trafficking, but appear to stabilize interdomain contacts to stimulate transport.","authors":"Sophie Achilles, Jan-Niklas Tomczak, Fabiane-Samira Baumann, Bassam G Haddad, Stefan Oswald, Jan-Philipp Machtens, Eric R Geertsma, Ilka Wittig, Georg Lamprecht","doi":"10.1152/ajpgi.00362.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00362.2024","url":null,"abstract":"<p><p>DRA (SLC26A3) is a major apical intestinal Cl<sup>-</sup>/HCO<sub>3</sub><sup>-</sup> exchanger, which is expressed in complex and hybrid N-glycosylated forms. While the importance of N-glycosylation is evident from the significantly reduced transport activity of non-N-glycosylated DRA constructs (DRA-N0), the underlying molecular mechanisms are controversial. Therefore, plasma membrane expression and lipid raft localization of glycosylation-deficient DRA-N0 were analyzed in HEK cells. The activity of DRA-N0 was reduced by 70% compared to the wildtype construct. Absolute expression of DRA-N0 was significantly reduced by approximately 57% in the cell lysate and by 34 and 45% in the plasma membrane and in plasma membrane-derived lipid rafts, respectively. These amounts are insufficient to account for the reduction in activity. Furthermore, the statistical analysis did not support a difference in the relative expression of DRA and DRA-N0 in the plasma membrane and in plasma membrane-derived lipid rafts, indicating that N-glycosylation does not affect transport activity through trafficking and localization in these cell compartments. To gain insight into potential intramolecular effects of N-glycosylation on DRA, its 3D-structure was predicted using AlphaFold3 with complex N-glycans covalently attached to N153, N161, and N164 in the transport domain. This revealed multiple inward- and outward-facing conformations of the protein. The number of interdomain contacts of the transport domain-bound glycans with the scaffold domain was higher in the inward-facing state. Because substrate release to the cytoplasm represents the rate-limiting step in many transport proteins, this suggests that in DRA glycans stabilize the inward-facing state facilitating anion transport.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273574","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}
引用次数: 0
Retatrutide Improves Steatohepatitis in an Accelerated Mouse Model of Diet-Induced Steatohepatitis with a Fructose Binge. 利曲鲁肽改善果糖暴食引起的脂肪性肝炎小鼠模型中的脂肪性肝炎。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-07 DOI: 10.1152/ajpgi.00164.2025
Greta Karoline Viebahn, Amit Khurana, Linton Freund, Daisy Chilin-Fuentes, Kristen Jepsen, Sara Brin Rosenthal, Shreyan Chatterjee, Volker Ellenrieder, Cynthia L Hsu, Bernd Schnabl, Phillipp Hartmann
{"title":"Retatrutide Improves Steatohepatitis in an Accelerated Mouse Model of Diet-Induced Steatohepatitis with a Fructose Binge.","authors":"Greta Karoline Viebahn, Amit Khurana, Linton Freund, Daisy Chilin-Fuentes, Kristen Jepsen, Sara Brin Rosenthal, Shreyan Chatterjee, Volker Ellenrieder, Cynthia L Hsu, Bernd Schnabl, Phillipp Hartmann","doi":"10.1152/ajpgi.00164.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00164.2025","url":null,"abstract":"<p><p>Fructose consumption contributes to metabolic dysfunction-associated steatohepatitis (MASH). Retatrutide is a novel triple receptor agonist that improves obesity and hepatic steatosis in humans. The aims of this study were to develop a shortened and clinically relevant dietary mouse model of diet-induced steatohepatitis, and to evaluate the effects of a retatrutide intervention in this model. C57BL/6N mice were subjected to a single fructose binge (10 mg/g body weight), or a new 31-day mouse model of diet-induced steatohepatitis using western diet, fructose and sucrose in the drinking water, and a final fructose binge with or without retatrutide. A single fructose binge resulted in significantly elevated alanine aminotransferase (ALT) and hepatic triglyceride levels in female mice after 6 hours; male mice showed less hepatotoxicity. The novel 31-day feeding model significantly increased body weight, ALT levels, hepatic triglycerides and cholesterol, and hepatic inflammatory markers in female and male mice compared with their chow-fed controls. The overall hepatic gene expression profile per RNA sequencing of treated mice correlated with that of human MASH in children and adults. Retatrutide intervention over the final 2 weeks of the 31-day mouse model significantly reduced body weight, ALT levels, hepatic triglycerides and cholesterol, and hepatic inflammatory markers in female mice compared with their vehicle-treated counterparts. Our findings indicate that female mice develop more severe liver injury due to a single fructose binge than males. The novel 31-day mouse model induces robust steatohepatitis and correlates with human disease. An intervention with retatrutide improves steatohepatitis in this shortened mouse model.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243593","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}
引用次数: 0
m6A mRNA Methylation Decorates Genes Involved in Fibrinogen Synthesis to Regulate Liver Regeneration in Mice. m6A mRNA甲基化修饰参与纤维蛋白原合成的基因以调节小鼠肝脏再生
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-07 DOI: 10.1152/ajpgi.00108.2025
Tomohiko Kimura, Dario F De Jesus, Hyunki Kim, Yi Zhang, Kazuki Fukuda, Jiang Hu, Giorgio Basile, Kimitaka Shibue, Kohei Kaku, Hideaki Kaneto, Rohit N Kulkarni
{"title":"m<sup>6</sup>A mRNA Methylation Decorates Genes Involved in Fibrinogen Synthesis to Regulate Liver Regeneration in Mice.","authors":"Tomohiko Kimura, Dario F De Jesus, Hyunki Kim, Yi Zhang, Kazuki Fukuda, Jiang Hu, Giorgio Basile, Kimitaka Shibue, Kohei Kaku, Hideaki Kaneto, Rohit N Kulkarni","doi":"10.1152/ajpgi.00108.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00108.2025","url":null,"abstract":"<p><p>The role of m<sup>6</sup>A RNA methylation in liver regeneration is unclear. This study aimed to determine the role of m<sup>6</sup>A methylation in liver regeneration after a 70% hepatectomy (HEPA) using liver specific Mettl 14 KO male mice. Analysis was conducted on post-operative days 1, 3, or 7 (HEPA1, 3, or 7) in control (Flox) mice. In Flox mice, CyclinD1 protein expression was highest on postoperative day 3 (HEPA3) consistent with a dynamic increase in hepatocyte replication. The abundance of Mettl14 protein presented a similar pattern on HEPA3. Then, we performed hepatectomy in Mettl14 KOs (M14KO) and Flox controls and observed significantly higher post-surgical mortality in mutants. In Flox mice, CyclinD1 protein levels and Ki67 were markedly increased on HEPA3 compared to SHAM, while being downregulated in M14KO. Characterizing the m<sup>6</sup>A epitranscriptomic changes in Flox mice after hepatectomy and contrasting them to hepatectomy in M14KO in HEPA3 revealed enrichment for gene ontology terms associated with endoplasmic reticulum, inflammation, and apoptosis. Differentially methylated genes in M14KO compared to Flox on HEPA3 were also enriched for PPAR and AMPK signaling. Finally, we identified hypomethylated transcripts involved in fibrinogen synthesis, such as Fga, Fgb, and Fgg, by comparing differentially m<sup>6</sup>A-decorated genes in M14KO versus Flox on HEPA3. Knockdown of fibrinogen leads to suppression of proliferation via activation of p21 protein in AML12 cells. Together, these data point to m<sup>6</sup>A RNA methylation being significant in decorating genes involved in fibrinogen synthesis in liver regeneration.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243613","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}
引用次数: 0
Hepatic protein kinase Cbeta antagonizing p38MAPK to activate ERK1/2 to dysregulate biliary lipid composition upon lithogenic stress. 肝蛋白激酶cβ拮抗剂p38MAPK激活ERK1/2,在致结石应激时失调胆脂组成。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-06 DOI: 10.1152/ajpgi.00208.2025
Yaoling Shu, Amit Rai, Gina M Sizemore, Michael Ostrowski, Wei Huang, Kamal D Mehta
{"title":"Hepatic protein kinase Cbeta antagonizing p38<sup>MAPK</sup> to activate ERK1/2 to dysregulate biliary lipid composition upon lithogenic stress.","authors":"Yaoling Shu, Amit Rai, Gina M Sizemore, Michael Ostrowski, Wei Huang, Kamal D Mehta","doi":"10.1152/ajpgi.00208.2025","DOIUrl":"https://doi.org/10.1152/ajpgi.00208.2025","url":null,"abstract":"<p><p>Lithogenic diet exposure disrupts biliary lipid homeostasis to promote precipitation of excess biliary cholesterol; however, the underlying pathogenic signaling mechanism remains unclear. Protein kinase Cbeta (PKCβ) is involved in regulating hepatic cholesterol and bile acid metabolism. In this study, we aimed to identify the initiating signaling and biological changes in the liver upon loss of hepatic PKCβ function under lithogenic stress. Transcriptome analysis of the liver revealed that hepatic deletion of PKCβ altered the expression of 183 liver genes, 118 of which were upregulated, and 65 were downregulated. We identified marked increases in the expression of genes involved in bile acid biosynthesis (<i>Cyp7a1</i> and <i>Cyp8b1</i>) and a decrease in retinol metabolism (<i>Cyp26b1</i>) as the most relevant changes, with blunted expression of genes involved in bile acid and phosphatidylcholine transporters. Mechanistic studies revealed that the hepatic PKCβ deficiency was associated with reduced ERK1/2 phosphorylation in concert with increased p38<sup>MAPK</sup> phosphorylation in the liver. Overexpression of PKCβ in the liver blocked p38<sup>MAPK</sup> activation as well as resulted in increased ERK1/2 phosphorylation and was accompanied by suppression of both <i>Cyp7a1</i> and <i>Cyp8b1</i> expression, demonstrating that hepatic PKCβ functions as a positive regulator of ERK1/2 to suppress expression of both genes by antagonizing p38<sup>MAPK</sup>. Furthermore, depletion of liver p38<sup>MAPK</sup> in PKCβ<sup>Hep-/-</sup> mice resulted in enhanced ERK1/2 phosphorylation and suppression of <i>Cyp7a1</i> and <i>Cyp8b1</i> expression. The findings yielded by this study support our understanding of the intricate interplay among PKCβ, p38<sup>MAPK</sup>, and ERK1/2 signaling <i>in vivo</i>, and provide valuable insights into potential therapeutic targets for the development of novel strategies to combat cholelithiasis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237719","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}
引用次数: 0
Colon: a likely middleman connecting the liver, adipose tissue, and gut microbiota in MASLD. 结肠:MASLD中连接肝脏、脂肪组织和肠道微生物群的可能中间人。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-09-15 DOI: 10.1152/ajpgi.00248.2025
Medha Priyadarshini, Brian T Layden
{"title":"Colon: a likely middleman connecting the liver, adipose tissue, and gut microbiota in MASLD.","authors":"Medha Priyadarshini, Brian T Layden","doi":"10.1152/ajpgi.00248.2025","DOIUrl":"10.1152/ajpgi.00248.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G559-G561"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12520229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068835","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}
引用次数: 0
Cyclic infusion mitigates liver dysfunction associated with continuous total parenteral nutrition in a novel murine model. 在一种新的小鼠模型中,循环输注减轻了与持续全肠外营养相关的肝功能障碍。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-08-11 DOI: 10.1152/ajpgi.00033.2025
Nathaniel B Willis, Tahliyah S Mims, Karen Antunes, Hubert Peng, Mei-I Yen, Chi-Liang Eric Yen, Joseph F Pierre
{"title":"Cyclic infusion mitigates liver dysfunction associated with continuous total parenteral nutrition in a novel murine model.","authors":"Nathaniel B Willis, Tahliyah S Mims, Karen Antunes, Hubert Peng, Mei-I Yen, Chi-Liang Eric Yen, Joseph F Pierre","doi":"10.1152/ajpgi.00033.2025","DOIUrl":"10.1152/ajpgi.00033.2025","url":null,"abstract":"<p><p>Parenteral nutrition (PN) is a lifesaving intervention for patients unable to feed enterally but is often associated with parenteral nutrition-associated liver disease (PNALD), also called intestinal failure-associated liver disease (IFALD). This disease is characterized by steatosis, cholestasis, and elevated liver stress markers. Continuous PN induces hepatic injury through mechanisms including insulin resistance, lipotoxicity, systemic inflammation, and oxidative stress. Infusion cycling is known to ameliorate clinical markers of liver injury, but metabolic underpinnings have not been thoroughly investigated. Therefore, we modeled PN-induced liver injury in mice to investigate how differential infusion patterns impacted hepatic metabolism. Intermittent infusions protected against increased circulating alanine aminotransferase levels and improved histopathology to more closely resemble chow controls. Transcriptomic analyses revealed 804 differentially expressed genes between PN groups, highlighting pathways related to peroxisome proliferator-activated receptor signaling, fatty acid metabolism, and peroxisomes. Relative to the continuous group, intermittent PN infusion specifically downregulated <i>Acaa1b</i>, <i>Aldh3a2</i>, <i>Inmt</i>, and <i>Acot4</i>; transcripts involved in peroxisomal lipid oxidation, dicarboxylic acid synthesis, and one-carbon metabolism. This study suggests that infusion cycling may attenuate metabolic burden induced by alternate lipid oxidation pathways. Future work can therapeutically leverage these metabolic pathways to deepen our understanding of PNALD/IFALD and guide PN treatments to improve patient outcomes.<b>NEW & NOTEWORTHY</b> This work demonstrated that the infusion schedule, independent of nutrient and caloric concentration, is a modulator of hepatic lipid metabolism in a novel murine model of parenteral nutrition. This cyclic infusion paradigm attenuated transcripts involved in microsomal and peroxisomal lipid oxidation, which were upregulated in the continuous infusion group. These data support the clinical use of cyclic infusion to improve hepatic parameters known to be adversely affected by parenteral nutrition.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G536-G545"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820389","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}
引用次数: 0
Neural control of goblet cells in the gastrointestinal tract. 胃肠道杯状细胞功能的神经控制。
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-08-18 DOI: 10.1152/ajpgi.00191.2025
Matthew C Rowe, Victor L Pettersson, Simona E Carbone, Jenny K Gustafsson, Daniel P Poole
{"title":"Neural control of goblet cells in the gastrointestinal tract.","authors":"Matthew C Rowe, Victor L Pettersson, Simona E Carbone, Jenny K Gustafsson, Daniel P Poole","doi":"10.1152/ajpgi.00191.2025","DOIUrl":"10.1152/ajpgi.00191.2025","url":null,"abstract":"<p><p>The mucus layer is an essential physical barrier that protects and lubricates mucosal surfaces in the body. The semipermeable nature of the mucus layer limits bacterial interactions with the epithelium while allowing nutrient absorption. Goblet cells (GCs) are specialized epithelial cells with a classical role to synthesize and secrete mucus to maintain the mucus layer. Emerging research has revealed the diverse nature of GC functions, including their interaction with the immune system through goblet cell-associated antigen passages to promote tolerance to dietary and bacterial antigens. Dysfunction of GCs or the mucus layer leaves the epithelium vulnerable to infection and is commonly associated with digestive disease. As such, there is a growing appreciation for the importance of GCs and the mucus layer to regulate mucosal homeostasis and protect against disease. Long-standing anatomical and pharmacological evidence indicates that the nervous system is a key regulator of GC function. However, the relative contribution from each division of the nervous system to the control of GC function is poorly defined. This is partly due to conflicting evidence from the literature and differences in experimental methods used. Furthermore, whether neurotransmitters influence GC functions and the associated mucus barrier directly or via indirect mechanisms, such as enhanced fluid secretion, remains unclear. The emergence of highly specific genetic approaches provides new opportunities to examine how specific nerve types can influence GC function. In this review, we consolidate the literature to date, with a focus on the stomach and lower gastrointestinal tract, and outline how current technologies may be useful to progress our fundamental understanding of neural-GC control.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G513-G535"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870823","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}
引用次数: 0
Probiotic-mediated regulation of arginine metabolism to improve intestinal barrier function: a metabolic makeover for IBD? 益生菌介导的精氨酸代谢调节改善肠屏障功能:IBD的代谢改造?
IF 3.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2025-10-01 Epub Date: 2025-09-15 DOI: 10.1152/ajpgi.00277.2025
Yevheniya Shevchenko, Michael A Schumacher
{"title":"Probiotic-mediated regulation of arginine metabolism to improve intestinal barrier function: a metabolic makeover for IBD?","authors":"Yevheniya Shevchenko, Michael A Schumacher","doi":"10.1152/ajpgi.00277.2025","DOIUrl":"10.1152/ajpgi.00277.2025","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G557-G558"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068889","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信