5,002 results match your criteria American journal of physiology. Gastrointestinal and liver physiology[Journal]


The renin-angiotensin system promotes colonic inflammation by inducing T17 activation via the JAK2/STAT pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 17. Epub 2019 Apr 17.

Medicine, The University of Chicago, United States.

Previous studies suggest that the renin-angiotensin system (RAS) is pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (Ang II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and Ang II levels were markedly increased in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Read More

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http://dx.doi.org/10.1152/ajpgi.00053.2019DOI Listing

Xenin-25 induces anion secretion by activating non-cholinergic secretomotor neurons in the rat ileum.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 12. Epub 2019 Apr 12.

Departments of Molecular Cell Physiology and Bio-Ionomics, Kyoto Prefectural University of Medicine, Japan.

Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the Xenin-25-induced anion secretion were characterized using Ussing chambered mucosa-submucosa preparation from the rat ileum. Read More

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http://dx.doi.org/10.1152/ajpgi.00333.2018DOI Listing

Inhibition of jejunal protein synthesis and breakdown in Pseudomonas aeruginosa induced sepsis pig model.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 12. Epub 2019 Apr 12.

Center for Translational Research in Aging & Longevity. Department of Health & Kinesiology, Texas A&M University, United States.

Maintenance of gut integrity has long been recognized as crucial for survival in sepsis but alterations in protein metabolism have not previously been documented. Therefore in the present study, we measured in a Pseudomonas aeruginosa induced porcine sepsis model, fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted conscious state.

Methods: FSR was measured by the incorporation rate of stable tracer amino acid (L-[ring-13C6]-phenylalanine) into tissue protein. Read More

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http://dx.doi.org/10.1152/ajpgi.00407.2018DOI Listing
April 2019
2 Reads

Elevated intracellular trypsin exacerbates acute pancreatitis and chronic pancreatitis in mice.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 3. Epub 2019 Apr 3.

Cancer Biology, Mayo Clinic, United States.

Intra-acinar trypsinogen activation occurs in the earliest stages of pancreatitis and is believed to play important roles in pancreatitis pathogenesis. However, the exact role of intra-acinar trypsin activity in pancreatitis remains elusive. Here, we aimed to examine the specific effects of intra-acinar trypsin activity on the development of pancreatitis using a transgenic mouse model. Read More

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http://dx.doi.org/10.1152/ajpgi.00004.2019DOI Listing
April 2019
5 Reads

microRNA-33a prevents epithelial-mesenchymal transition, invasion and metastasis of gastric cancer cells through the Snail/Slug pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 3. Epub 2019 Apr 3.

the Second Affiliated Hospital of Wenzhou Medical University, China.

Invasion and metastasis are responsible for the majority of deaths in gastric cancer (GC). microRNA-33a (miR-33a)might function as a tumor suppressor in multiple cancers. Here, we describe the regulation and function of miR-33a in GC and mechanisms involved in epithelial-mesenchymal transition (EMT) and metastasis. Read More

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http://dx.doi.org/10.1152/ajpgi.00284.2018DOI Listing

Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Janssen Pharmaceutical R&D, United States.

Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia and dyslipidemia in obese rats; however, the mechanisms for this are largely unknown. We reasoned that CS creates an apparent dietary protein restriction, which is known to increase hepatic fibroblast growth factor 21 (FGF21). Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00404.2018
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http://dx.doi.org/10.1152/ajpgi.00404.2018DOI Listing
March 2019
3 Reads

TCF21 inhibits tumor-associated angiogenesis and suppresses the growth of cholangiocarcinoma by targeting PI3K/Akt and ERK signaling.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Hunan Provincial People's Hospital and the First Affiliated Hospital of Hunan Normal University, China.

Background: Tumor-associated angiogenesis plays a critical role in the pathogenesis of cholangiocarcinoma (CCA). In this study, we examined the biological effects and molecular mechanisms of transcription factor 21 (TCF21) on CCA-associated angiogenesis.

Methods: TCF21 expression was compared between 15 pairs of para-tumor normal tissues and CCA tissues, and also between normal bile duct epithelial cells and two CCA cell lines, QBC-939 and TFK-1 using real-time PCR and Western blot. Read More

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http://dx.doi.org/10.1152/ajpgi.00264.2018DOI Listing
March 2019
2 Reads

Differential Action of TGR5 Agonists on GLP-2 Secretion and Promotion of Intestinal Adaptation in Piglet Short Bowel Model.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, United States.

Enteroendocrine L cells and GLP-2 secretion are activated in the intestinal adaptation process following bowel resection in short bowel patients. Our aim was to assess whether enteral activation of Takeda G-protein-coupled receptor 5 (TGR5) expressed in enteroendocrine L cells could augment endogenous GLP-2 secretion and the intestinal adaptation response in a piglet model. In study 1, parenterally-fed, neonatal pigs (n=6/group) were gavaged with vehicle, olive extract (OE) at 10 or 50 mg/kg, or ursolic acid (UA) 10 mg/kg and plasma GLP-2 were measured for 6 hr. Read More

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http://dx.doi.org/10.1152/ajpgi.00360.2018DOI Listing
March 2019
3.798 Impact Factor

FXR agonist GW4064 improves the liver and intestinal pathology and alters bile acid metabolism in rats undergoing small intestinal resection.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, China.

Mortality associated with liver disease was observed in patients with short bowel syndrome (SBS); however, its mechanism remains unclear. Bile acid (BA) dysmetabolism may be one of the putative mechanisms, and farnesoid X receptor (FXR) is the key regulator of BA synthesis. Here, we showed that in a rat model of small bowel resection associated with liver disease (SBR-ALD), BA composition of hepatic tissues reflected a larger proportion of primary and secondary unconjugated BAs, and those of colon contents and serum showed an increased ratio of secondary unconjugated BAs. Read More

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http://dx.doi.org/10.1152/ajpgi.00356.2017DOI Listing

Electroacupuncture via Chronically Implanted Electrodes Improves Gastrointestinal Motility by Balancing Sympathovagal Activities in a Rat Model of Constipation.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Division of Gastroenterology and Hepatology, Johns Hopkins University, United States.

Background: Electroacupuncture (EA) has been reported for treating constipation in clinical studies. However, little is known on possible mechanisms involved in the prokinetic effect of EA.

Aims: To investigate the effects and underlying autonomic mechanisms of EA via chronically implanted electrodes for constipation rat induced by Loperamide (Lop). Read More

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http://dx.doi.org/10.1152/ajpgi.00018.2018DOI Listing
March 2019
1 Read

Effect of bacterial flagellin on thiamin uptake by human and mouse pancreatic acinar cells: Inhibition mediated at the level of transcription of THTR-1 and 2.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Departments of Physiology/Biophysics and Medicine, School of Medicine, University of California, Irvine, CA, 92697; Veterans Affairs Medical Center, Long Beach, CA, 90822, United States.

Thiamin (vitamin B1) is essential for normal cellular metabolism and function. Pancreatic acinar cells (PACs) obtain thiamin from circulation, via a specific carrier-mediated process that involves the plasma membrane thiamin transporters -1 and -2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3 genes, respectively). There is nothing known about the effect of bacterial products/toxins on thiamin uptake by PACs. Read More

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http://dx.doi.org/10.1152/ajpgi.00048.2019DOI Listing
March 2019
3.798 Impact Factor

Translational and transcriptional responses in human primary hepatocytes under hypoxia.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Center for Biologics Evaluation and Research, US Food and Drug Administration, United States.

The liver is the primary source of a large number of plasma proteins and plays a critical role in multiple biological processes. Inadequate oxygen supply characterizing various clinical settings such as liver transplantation exposes the liver to hypoxic conditions. Studies assessing hypoxia-induced global translational changes in liver are lacking. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00331.2018
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http://dx.doi.org/10.1152/ajpgi.00331.2018DOI Listing
March 2019
7 Reads

Multi-transcriptomes analyses reveal prioritized genes specifically associated with liver fibrosis progression independent of etiology.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

Beijing Friendship Hospital, Capital Medical University, China.

Elimination or suppression of causative factors can raise the possibility of liver fibrosis regression. However, different injurious stimuli will give fibrosis from somewhat different etiologies, which, in-turn, may hamper the discovery of liver fibrosis-specific therapeutic drugs. Therefore, the analogical cellular and molecular events shared by various etiologies-evoked liver fibrosis should be clarified. Read More

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http://dx.doi.org/10.1152/ajpgi.00339.2018DOI Listing
March 2019
1 Read

Intra-pancreatic fat deposition and visceral fat volume are associated with the presence of diabetes after acute pancreatitis.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 28. Epub 2019 Mar 28.

University of Auckland, New Zealand.

Ectopic fat and abdominal adiposity phenotypes have never been investigated holistically in individuals after acute pancreatitis (AP). The aim of the study was to investigate phenotypic differences in ectopic fat and abdominal fat between individuals after AP (with and without diabetes) and to determine the role of pancreatitis-related factors. Eighty-four individuals were studied cross-sectionally in, on average, 21 months since last episode of AP and were categorized into 'diabetes' and 'no diabetes' groups. Read More

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http://dx.doi.org/10.1152/ajpgi.00385.2018DOI Listing

Portal milieu and the interplay of multiple anti-diabetic effects after gastric bypass surgery.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 21. Epub 2019 Mar 21.

Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, United States.

Aims: Diabetes is a worldwide health problem. Roux-en-Y-Gastric-Bypass (RYGB) leads to rapid resolution of Type-2-Diabetes (T2D). Decreased hepatic insulin resistance is key but underlying mechanisms are poorly understood. Read More

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http://dx.doi.org/10.1152/ajpgi.00389.2018DOI Listing
March 2019
1 Read

Wnt signaling inhibition by monensin results in a period of Hippo pathway activation during intestinal adaptation in zebrafish.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 21. Epub 2019 Mar 21.

Surgery, Childrens Hospital Los Angeles/The Saban Research Institute, United States.

Introduction: Intestinal adaptation (IA) is a critical response to increase epithelial surface area after intestinal loss. Short bowel syndrome (SBS) may follow massive intestinal resection in human patients, particularly without adequate IA. We previously validated a model in zebrafish (ZF) that recapitulates key SBS pathophysiologic features. Read More

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http://dx.doi.org/10.1152/ajpgi.00343.2018DOI Listing

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 14. Epub 2019 Mar 14.

Department of General, Visceral- and Transplantation Surgery, Charité - Universitätsmedizin Berlin.

Dynamic liver function assessment by the C-methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic CYP1A2 activity. One proven strategy for preoperative risk assessement in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. Read More

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http://dx.doi.org/10.1152/ajpgi.00335.2018DOI Listing
March 2019
1 Read

The anti-tumour effects of all-trans retinoic acid and its synergism with gemcitabine are associated with down-regulation of p21-activated kinases in pancreatic cancer.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 7. Epub 2019 Mar 7.

University of Melbourne, Australia.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies worldwide. All-trans retinoic acide (ATRA) has been used as an anti-stromal agent in PDA, and its anti-tumour effect has also been reported in various kinds of cancer, including PDA. Inhibition of p21-activated kinases (PAKs) is associated with decreased tumour growth and increased gemcitabine sensitivity. Read More

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http://dx.doi.org/10.1152/ajpgi.00344.2018DOI Listing

TO901317 inhibits the development of Hepatocellular Carcinoma by LXRα/Glut1 decreasing the glycometabolism.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 28. Epub 2019 Feb 28.

Institute of Pharmacy and Pharmacology, University of South China, China.

To observe the effect and possible mechanism of TO901317 in vivo and in vitro to provide a new basis for the targeted therapy of Hepatocellular carcinoma (HCC). The expression of LXRα, Glut1, PCNA and MMP9 were analyzed from the HCC public database. The result showed that LXRα was down-regulated, whereas Glut1, PCNA and MMP9 were up-regulated in human HCC compared with normal liver. Read More

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http://dx.doi.org/10.1152/ajpgi.00061.2018DOI Listing
February 2019

Interplay of spinal and vagal pathways on esophageal acid-related anterior cingulate cortex functional networks in rats.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 28. Epub 2019 Feb 28.

Division of Gastroenterology & Hepatology, Medical College of Wisconsin, United States.

Background & Aims: Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on the esophageal acid-related functional connectivity has been elusive. The aim is to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis. Read More

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http://dx.doi.org/10.1152/ajpgi.00228.2018DOI Listing
February 2019

Intestinal iNKT cells migrate to liver and contribute to hepatocyte apoptosis during alcoholic liver disease.

Am J Physiol Gastrointest Liver Physiol 2019 May 28;316(5):G585-G597. Epub 2019 Feb 28.

Department of Medicine, University of California San Diego , La Jolla, California.

We investigated the migration of intestinal immune cells to the liver and their contribution to alcoholic liver disease. In mice fed ethanol, we found that an increased number of invariant natural killer T (iNKT) cells, which respond to the antigen presented by CD1d, migrated from mesenteric lymph nodes to the liver. iNKT cells react to lipid antigens, so we studied their activities in mice with intestinal epithelial cell-specific deletion of () as a model for altering intestinal lipidomic profiles. Read More

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http://dx.doi.org/10.1152/ajpgi.00269.2018DOI Listing
May 2019
2 Reads

Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing β-oxidation of fatty acid in mice.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 21;316(4):G527-G538. Epub 2019 Feb 21.

Tianjin Key Laboratory of Metabolic Diseases; Key Laboratory of Immune Microenvironment and Disease (Ministry of Education); Collaborative Innovation Center of Tianjin for Medical Epigenetics and Department of Physiology and Pathophysiology, Tianjin Medical University , Tianjin , China.

Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. Read More

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http://dx.doi.org/10.1152/ajpgi.00148.2018DOI Listing
April 2019
2 Reads

Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents.

Am J Physiol Gastrointest Liver Physiol 2019 May 15;316(5):G574-G584. Epub 2019 Feb 15.

Novo Nordic Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00010.2019
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http://dx.doi.org/10.1152/ajpgi.00010.2019DOI Listing
May 2019
15 Reads
3.798 Impact Factor

Mucosal RNA and Protein Expression as the next frontier in IBS: abnormal function despite morphologically intact small intestinal Mucosa.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

University Hospital Vall d'Hebron, Barcelona.

Irritable bowel syndrome is one of the commonest gastrointestinal disorders. Although long-time considered a pure functional disorder, intense research in past years has rendered a very complex and varied array of observations indicating the presence of structural and molecular abnormalities underlying characteristic motor and sensitive changes and clinical manifestations. Analysis of gene and protein expression in the intestinal mucosa has shed light on the molecular mechanisms implicated in IBS physiopathology. Read More

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http://dx.doi.org/10.1152/ajpgi.00186.2018DOI Listing
February 2019
1 Read

Gut microbiota in liver disease: too much is harmful, nothing at all is not helpful either.

Am J Physiol Gastrointest Liver Physiol 2019 May 15;316(5):G563-G573. Epub 2019 Feb 15.

Department of Medicine, University of California, San Diego, La Jolla, California.

The intestinal microbiome plays a major role in the pathogenesis of liver disease, with a hallmark event being dysbiosis, or an imbalance of pathobionts and beneficial bacteria with the associated deleterious effects on their host. Reducing the number of intestinal bacteria with antibiotic treatment is generally advantageous in experimental liver diseases. Complete absence of intestinal microbiota as in germ-free rodents can be protective in autoimmune hepatitis and hepatic tumors induced by chemicals, or it can exacerbate disease as in acute toxic liver injury and liver fibrosis/cirrhosis. Read More

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http://dx.doi.org/10.1152/ajpgi.00370.2018DOI Listing
May 2019
3 Reads

The Role of Ketone Signaling in the Hepatic Response to Fasting.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 15. Epub 2019 Feb 15.

School of Animal and Comparative Biomedical Scieces, U. Arizona, United States.

Ketosis is a metabolic adaptation to fasting, non-alcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G-protein coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. Read More

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http://dx.doi.org/10.1152/ajpgi.00415.2017DOI Listing
February 2019
4 Reads

Necrostatin-1 accelerates time to death in a rat model of cecal ligation and puncture and massively increases hepatocyte caspase-3 cleavage.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 8;316(4):G551-G561. Epub 2019 Feb 8.

Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Peoples Republic of China.

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Read More

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http://dx.doi.org/10.1152/ajpgi.00175.2018DOI Listing

Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 8. Epub 2019 Feb 8.

ADEN group EA 4311, Rouen University, France.

Background: Inflammatory bowel diseases (IBD) are characterized by flares repetition and remission periods leading to chronic post-inflammatory sequels. Among them, one third of IBD patients are suffering from persisting functional symptoms or psychological comorbidities during remission. Our study aimed to assess functional and behavioral sequels of chronic colitis in rats with quiescent intestinal inflammation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00248.2018
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http://dx.doi.org/10.1152/ajpgi.00248.2018DOI Listing
February 2019
6 Reads

lncRNA GAS5 restrains CCl-induced hepatic fibrosis by targeting miR-23a through the PTEN/PI3K/Akt signaling pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 8;316(4):G539-G550. Epub 2019 Feb 8.

College of Traditional Mongolia Medicine, Inner Mongolia Medical University , Hohhot, Inner Mongolia , People's Republic of China.

Hepatic fibrosis is chronic liver damage with many causes that has a relatively high death rate. The current study showed that long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5), microRNA-23a (miR-23a), and phosphatase and tensin homolog (PTEN) play important roles in the pathological process of hepatic fibrosis but have a relatively unclear regulatory mechanism. This study aimed to investigate the roles of lncRNA GAS5, miR-23a, and PTEN in the pathological process of hepatic fibrosis and hepatic stellate cell (HSC) activation. Read More

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http://dx.doi.org/10.1152/ajpgi.00249.2018DOI Listing
April 2019
3 Reads

Preservation of reserve intestinal epithelial stem cells following severe ischemic injury.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 4;316(4):G482-G494. Epub 2019 Feb 4.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University , Raleigh, North Carolina.

Intestinal ischemia is an abdominal emergency with a mortality rate >50%, leading to epithelial barrier loss and subsequent sepsis. Epithelial renewal and repair after injury depend on intestinal epithelial stem cells (ISC) that reside within the crypts of Lieberkühn. Two ISC populations critical to epithelial repair have been described: 1) active ISC (aISC; highly proliferative; leucine-rich-repeat-containing G protein-coupled receptor 5 positive, sex determining region Y-box 9 positive) and 2) reserve ISC [rISC; less proliferative; homeodomain only protein X (Hopx)]. Read More

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http://dx.doi.org/10.1152/ajpgi.00262.2018DOI Listing
April 2019
3 Reads

Ethanol withdrawal mitigates fatty liver by normalizing lipid catabolism.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 4;316(4):G509-G518. Epub 2019 Feb 4.

The Liver Study Unit, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.

We are investigating the changes in hepatic lipid catabolism that contribute to alcohol-induced fatty liver. Following chronic ethanol (EtOH) exposure, abstinence from alcohol resolves steatosis. Here, we investigated the hepatocellular events that lead to this resolution by quantifying specific catabolic parameters that returned to control levels after EtOH was withdrawn. Read More

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http://dx.doi.org/10.1152/ajpgi.00376.2018DOI Listing
April 2019
3 Reads
3.798 Impact Factor

Chronic alcohol exposure alters circulating insulin and ghrelin levels: role of ghrelin in hepatic steatosis.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 31;316(4):G453-G461. Epub 2019 Jan 31.

Department of Internal Medicine, University of Nebraska Medical Center , Omaha, Nebraska.

Fatty liver is the earliest response of the liver to excessive ethanol consumption. Central in the development of alcoholic steatosis is increased mobilization of nonesterified free fatty acids (NEFAs) to the liver from the adipose tissue. In this study, we hypothesized that ethanol-induced increase in ghrelin by impairing insulin secretion, could be responsible for the altered lipid metabolism observed in adipose and liver tissue. Read More

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http://dx.doi.org/10.1152/ajpgi.00334.2018DOI Listing
April 2019
2 Reads

Differential biomechanical properties of mouse distal colon and rectum innervated by the splanchnic and pelvic afferents.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 31;316(4):G473-G481. Epub 2019 Jan 31.

Department of Biomedical Engineering, University of Connecticut , Storrs, Connecticut.

Visceral pain is one of the principal complaints of patients with irritable bowel syndrome, and this pain is reliably evoked by mechanical distension and stretch of distal colon and rectum (colorectum). This study focuses on the biomechanics of the colorectum that could play critical roles in mechanical neural encoding. We harvested the distal 30 mm of the colorectum from mice, divided evenly into three 10-mm-long segments (colonic, intermediate and rectal), and conducted biaxial mechanical stretch tests and opening-angle measurements for each tissue segment. Read More

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http://dx.doi.org/10.1152/ajpgi.00324.2018DOI Listing
April 2019
1 Read

G protein-coupled receptor trafficking and signaling: new insights into the enteric nervous system.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 31;316(4):G446-G452. Epub 2019 Jan 31.

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences and Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University , Parkville, Victoria , Australia.

G protein-coupled receptors (GPCRs) are essential for the neurogenic control of gastrointestinal (GI) function and are important and emerging therapeutic targets in the gut. Detailed knowledge of both the distribution and functional expression of GPCRs in the enteric nervous system (ENS) is critical toward advancing our understanding of how these receptors contribute to GI function during physiological and pathophysiological states. Equally important, but less well defined, is the complex relationship between receptor expression, ligand binding, signaling, and trafficking within enteric neurons. Read More

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http://dx.doi.org/10.1152/ajpgi.00406.2018DOI Listing

Topographical plots of esophageal distension and contraction: effects of posture on esophageal peristalsis and bolus transport.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 24;316(4):G519-G526. Epub 2019 Jan 24.

Division of Gastroenterology, Department of Medicine, University of California San Diego , San Diego, California.

Each swallow induces a wave of inhibition followed by contraction in the esophagus. Unlike contraction, which can easily be measured in humans using high-resolution manometry (HRM), inhibition is difficult to measure. Luminal distension is a surrogate of the esophageal inhibition. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00397.2018
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http://dx.doi.org/10.1152/ajpgi.00397.2018DOI Listing
April 2019
4 Reads

Hepatic transcriptome signatures in patients with varying degrees of nonalcoholic fatty liver disease compared with healthy normal-weight individuals.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 17;316(4):G462-G472. Epub 2019 Jan 17.

Department of Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. Read More

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http://dx.doi.org/10.1152/ajpgi.00358.2018DOI Listing
April 2019
3 Reads

Defective FXR-FGF15 signaling and bile acid homeostasis in cystic fibrosis mice can be restored by the laxative polyethylene glycol.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 17;316(3):G404-G411. Epub 2019 Jan 17.

Section of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.

The gastrointestinal phenotype of cystic fibrosis (CF) features intestinal bile acid (BA) malabsorption, impaired intestinal farnesoid X receptor (FXR) activation, and consequently reduced fibroblast growth factor 19 (FGF19, FGF15 in mice) production. The osmotic laxative polyethylene glycol (PEG) has been shown to decrease intestinal mucus accumulation in CF mice and could, by doing so, improve BA reabsorption. Here we determined the effect of PEG on BA excretion and FXR-FGF15 signaling in CF mice. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00188.2018
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http://dx.doi.org/10.1152/ajpgi.00188.2018DOI Listing
March 2019
15 Reads

AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G387-G396. Epub 2019 Jan 10.

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University , Fuzhou , China.

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNF-α-induced hepatocyte apoptosis and liver injury. Read More

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http://dx.doi.org/10.1152/ajpgi.00350.2018DOI Listing
March 2019
3 Reads

Histamine-mediated potentiation of transient receptor potential (TRP) ankyrin 1 and TRP vanilloid 4 signaling in submucosal neurons in patients with irritable bowel syndrome.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G338-G349. Epub 2019 Jan 10.

Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven , Leuven , Belgium.

Previously, we showed histamine-mediated sensitization of transient receptor potential (TRP) vanilloid 1 (TRPV1) in patients with irritable bowel syndrome (IBS). Sensitization of TRP ankyrin 1 (TRPA1) and TRP vanilloid 4 (TRPV4) are also involved in aberrant pain perception in preclinical models of somatic pain. Here, we hypothesize that in parallel with TRPV1, histamine sensitizes TRPA1 and TRPV4, contributing to increased visceral pain in patients with IBS. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00116.2018
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http://dx.doi.org/10.1152/ajpgi.00116.2018DOI Listing
March 2019
2 Reads

Decreased electrogenic anionic secretory response in the porcine colon following in vivo challenge with Brachyspira spp. supports an altered mucin environment.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 10;316(4):G495-G508. Epub 2019 Jan 10.

Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan , Saskatoon , Canada.

Brachyspira spp. cause diarrheal disease in multiple animal species by colonization of the colon, resulting in colitis, mucus induction, and disrupted ion transport. Unique to spirochete pathogenesis is the immense production of mucus, resulting in a niche mucin environment likely favoring spirochete colonization. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00348.2018
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http://dx.doi.org/10.1152/ajpgi.00348.2018DOI Listing
April 2019
9 Reads

Dietary cholesterol and apolipoprotein A-I are trafficked in endosomes and lysosomes in the live zebrafish intestine.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 10;316(3):G350-G365. Epub 2019 Jan 10.

Department of Embryology, Carnegie Institution for Science , Baltimore, Maryland.

Difficulty in imaging the vertebrate intestine in vivo has hindered our ability to model nutrient and protein trafficking from both the lumenal and basolateral aspects of enterocytes. Our goal was to use live confocal imaging to increase understanding of intestinal trafficking of dietary cholesterol and apolipoprotein A-I (APOA-I), the main structural component of high-density lipoproteins. We developed a novel assay to visualize live dietary cholesterol trafficking in the zebrafish intestine by feeding TopFluor-cholesterol (TF-cholesterol), a fluorescent cholesterol analog, in a lipid-rich, chicken egg yolk feed. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00080.2018
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http://dx.doi.org/10.1152/ajpgi.00080.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415739PMC
March 2019
15 Reads

Intestinal TGR5 agonism improves hepatic steatosis and insulin sensitivity in Western diet-fed mice.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 3;316(3):G412-G424. Epub 2019 Jan 3.

Ardelyx, Incorporated, Fremont, California.

Takeda G protein-coupled receptor 5 (TGR5) agonists induce systemic release of glucagon-like peptides (GLPs) from intestinal L cells, a potentially therapeutic action against metabolic diseases such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), and Type 2 diabetes. Historically, TGR5 agonist use has been hindered by side effects, including inhibition of gallbladder emptying. Here, we characterize RDX8940, a novel, orally administered TGR5 agonist designed to have minimal systemic effects and investigate its activity in mice fed a Western diet, a model of NAFLD and mild insulin resistance. Read More

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http://dx.doi.org/10.1152/ajpgi.00300.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459286PMC
March 2019
3 Reads
3.798 Impact Factor

Pancreatic and mucosal enzymes in choline phospholipid digestion.

Am J Physiol Gastrointest Liver Physiol 2019 Apr 21;316(4):G425-G445. Epub 2018 Dec 21.

Gastroenterology and Nutrition Laboratory, Department of Clinical Sciences, Lund University , Lund , Sweden.

The digestion of choline phospholipids is important for choline homeostasis, lipid signaling, postprandial lipid and energy metabolism, and interaction with intestinal bacteria. The digestion is mediated by the combined action of pancreatic and mucosal enzymes. In the proximal small intestine, hydrolysis of phosphatidylcholine (PC) to 1-lyso-PC and free fatty acid (FFA) by the pancreatic phospholipase A IB coincides with the digestion of the dietary triacylglycerols by lipases, but part of the PC digestion is extended and must be mediated by other enzymes as the jejunoileal brush-border phospholipase B/lipase and mucosal secreted phospholipase A X. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00320.2018
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http://dx.doi.org/10.1152/ajpgi.00320.2018DOI Listing
April 2019
18 Reads

Ghrelin acylation by ghrelin- O-acyltransferase can occur in healthy part of oncological liver in humans.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 21;316(3):G366-G371. Epub 2018 Dec 21.

Division of Endocrinology, CHU Saint-Etienne, Saint-Etienne , France.

Activation of ghrelin is controlled by the enzyme ghrelin- O-acyl transferase (GOAT). In humans, localization of this acylation is poorly understood. The aim of this study is to explore GOAT localization and activation in the human liver by evaluating both bioactive and non-bioactive ghrelin in the bloodstream entering and leaving the liver and to simultaneously evaluate GOAT mRNA expression in the liver. Read More

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http://dx.doi.org/10.1152/ajpgi.00143.2018DOI Listing
March 2019
1 Read

Enterotoxigenic Escherichia coli heat labile enterotoxin inhibits intestinal ascorbic acid uptake via a cAMP-dependent NF-κB-mediated pathway.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 4;316(1):G55-G63. Epub 2018 Oct 4.

Department of Medicine, University of California , Irvine, California.

Vitamin C is an antioxidant and acts as a cofactor for many enzymatic reactions. Humans obtain vitamin C from dietary sources via intestinal absorption, a process that involves the sodium-dependent vitamin C transporters-1 and -2 (SVCT1 and SVCT2). Enterotoxigenic Escherichia coli (ETEC) infection impacts intestinal absorption/secretory functions, but nothing is known about its effect on ascorbic acid (AA) uptake. Read More

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http://dx.doi.org/10.1152/ajpgi.00259.2018DOI Listing
January 2019
1 Read

Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds.

Am J Physiol Gastrointest Liver Physiol 2019 Jan 8;316(1):G15-G24. Epub 2018 Nov 8.

Bristol-Myers Squibb, Pennington, New Jersey.

Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the antifibrotic effect of experimental compounds in a physiological environment. In this study using RNA sequencing, we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00281.2018
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http://dx.doi.org/10.1152/ajpgi.00281.2018DOI Listing
January 2019
11 Reads

Introduction to themed series on intestinal stem cells and the NIDDK Intestinal Stem Cell Consortium.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 14;316(2):G247-G250. Epub 2018 Dec 14.

Department of Diabetes and Cancer Discovery Science, City of Hope Comprehensive Cancer Center, Duarte, California.

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http://dx.doi.org/10.1152/ajpgi.00146.2018DOI Listing
February 2019
1 Read

Provocative testing in patients with jackhammer esophagus: evidence for altered neural control.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 13;316(3):G397-G403. Epub 2018 Dec 13.

Department of Pathophysiology and Transplantation, Università degli Studi di Milano , Milan , Italy.

Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high-resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction, respectively. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 men; median age: 63 yr; IQR: 54-70 yr). Read More

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https://www.physiology.org/doi/10.1152/ajpgi.00342.2018
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http://dx.doi.org/10.1152/ajpgi.00342.2018DOI Listing
March 2019
5 Reads

Liver repair and regeneration after ischemia-reperfusion injury is associated with prolonged fibrosis.

Am J Physiol Gastrointest Liver Physiol 2019 Mar 13;316(3):G323-G331. Epub 2018 Dec 13.

Department of Surgery, College of Medicine, University of Cincinnati , Cincinnati, Ohio.

Liver recovery after hepatic ischemia-reperfusion (I/R) injury is characterized by clearance of dead tissue and its replacement with functional liver parenchyma. Previous reports have observed fibrosis after liver I/R. To determine whether liver fibrosis after I/R was a pathologic consequence of the injury response, we assessed the development of liver fibrosis after I/R and its impact on subsequent insult. Read More

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http://dx.doi.org/10.1152/ajpgi.00154.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459287PMC
March 2019
1 Read

MMP-9-induced increase in intestinal epithelial tight permeability is mediated by p38 kinase signaling pathway activation of MLCK gene.

Am J Physiol Gastrointest Liver Physiol 2019 Feb 13;316(2):G278-G290. Epub 2018 Dec 13.

Penn State Milton S. Hershey Medical Center, College of Medicine , Hershey, Pennsylvania.

Matrix metalloproteinase-9 (MMP-9) has been implicated as being an important pathogenic factor in inflammatory bowel disease (IBD). MMP-9 is markedly elevated in intestinal tissue of patients with IBD, and IBD patients have a defective intestinal tight-junction (TJ) barrier manifested by an increase in intestinal permeability. The loss of intestinal epithelial barrier function is an important contributing factor in the development and prolongation of intestinal inflammation; however, the role of MMP-9 in intestinal barrier function remains unclear. Read More

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http://dx.doi.org/10.1152/ajpgi.00126.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397336PMC
February 2019
1 Read