AJP: Gastrointestinal and Liver Physiology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Hydrophobic bile acid apoptosis is regulated by sphingosine-1-phosphate receptor 2 in rat hepatocytes and human hepatocellular carcinoma cells
In conclusion, SIPR2 inhibition attenuates GCDC-induced apoptosis and inhibits and augments GCDC-induced JNK and Akt phosphorylation, respectively. In addition, GCDC must enter hepatocytes to mediate cell death or activate kinases. These results suggest that SIPR2 activation is proapoptotic in GCDC-induced cell death but that this effect is not due to direct ligation of the S1PR2 by the bile acid. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Webster, C. R. L., Anwer, M. S. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Prevention of gallbladder hypomotility via FATP2 inhibition protects from lithogenic diet-induced cholelithiasis
Gallstone disease is a widespread disorder costing billions for annual treatment in the United States. The primary mechanisms underlying gallstone formation are biliary cholesterol supersaturation and gallbladder hypomotility. The relative contribution of these two processes has been difficult to dissect, as experimental lithogenic diets cause both bile supersaturation and alterations in gallbladder motility. Importantly, there is no mechanistic explanation for obesity as a major risk factor for cholelithiasis. We discovered that lithogenic diets induce ectopic triacylglycerol (TAG) accumulation, a major feature of obesity...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Tharp, K. M., Khalifeh-Soltani, A., Park, H. M., Yurek, D. A., Falcon, A., Wong, L., Feng, R., Atabai, K., Stahl, A. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Intestinal inflammation requires FOXO3 and prostaglandin E2-dependent lipogenesis and elevated lipid droplets
Intestinal inflammation has been recently characterized by the dysregulation of lipids as metabolic and energy sources, revealing a novel feature of its pathophysiology. Because intracellular lipids, stored in dynamic lipid droplets (LDs), provide energy for cellular needs, we investigated whether they play a role in intestinal inflammation. In the inflamed intestine of mice, elevated LDs were found in colonic and infiltrating immune cells as shown by staining for the LD coat protein PLIN2 and for lipids with BODIPY. In colonic cells, TNF stimulated LD increases by receptor signaling rely on phosphatidylinositol 3-kinase a...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Heller, S., Cable, C., Penrose, H., Makboul, R., Biswas, D., Cabe, M., Crawford, S. E., Savkovic, S. D. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Fibroblast growth factor 21 and exercise-induced hepatic mitochondrial adaptations
In conclusion, FGF21 does not appear necessary for exercise-induced systemic and hepatic mitochondrial adaptations, but the increased adiposity, hyperinsulinemia, and impairments in hepatic mitochondrial function induced by FGF21 deficiency can be partially rescued by daily wheel running exercise. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Fletcher, J. A., Linden, M. A., Sheldon, R. D., Meers, G. M., Morris, E. M., Butterfield, A., Perfield, J. W., Thyfault, J. P., Rector, R. S. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages
The short-chain fatty acid butyrate is produced by fermentation of dietary fiber by the intestinal microbiota; butyrate is the primary energy source of colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized that butyrate would reinforce an M(IL-4) phenotype. Here, we show that in the presence of butyrate M(IL-4)s display reduced expression of their hallmark markers Arg1 and Ym1 and significantly suppressed LPS-induced nitric oxide, IL-12p40, and IL-10 production. Butyrate treatment likely altered the M(IL-4) phenotype via inhibit...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Fernando, M. R., Saxena, A., Reyes, J.-L., McKay, D. M. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

MAG-EPA reduces severity of DSS-induced colitis in rats
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations....
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Morin, C., Blier, P. U., Fortin, S. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

Enhanced ethanol catabolism in orphan nuclear receptor SHP-null mice
Deficiency of the orphan nuclear hormone receptor small heterodimer partner (SHP, NR0B2) protects mice from diet-induced hepatic steatosis, in part, via repression of peroxisome proliferator-activated receptor (PPAR)-2 (Pparg2) gene expression. Alcoholic fatty liver diseases (AFLD) share many common pathophysiological features with non-AFLD. To study the role of SHP and PPAR2 in AFLD, we used a strategy of chronic ethanol feeding plus a single binge ethanol feeding to challenge wild-type (WT) and SHP-null (SHP–/–) mice with ethanol. The ethanol feeding induced liver fat accumulation and mRNA expression of hepat...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Park, J. E., Lee, M., Mifflin, R., Lee, Y. K. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Optogenetic activation of mechanically insensitive afferents in mouse colorectum reveals chemosensitivity
The sensory innervation of the distal colorectum includes mechanically insensitive afferents (MIAs; ~25%), which acquire mechanosensitivity in persistent visceral hypersensitivity and thus generate de novo input to the central nervous system. We utilized an optogenetic approach to bypass the process of transduction (generator potential) and focus on transformation (spike initiation) at colorectal MIA sensory terminals, which is otherwise not possible in typical functional studies. From channelrhodopsin2-expressing mice (driven by Advillin-Cre), the distal colorectum with attached pelvic nerve was harvested for ex vivo sing...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Feng, B., Joyce, S. C., Gebhart, G. F. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity
In this study, we used the rat mesenteric collecting vessel as an in vivo model to quantify the effect of lipoproteins on vessel function. Lipid load was continuously monitored by using the intensity of a fluorescent fatty-acid analog, which we infused along with a fat emulsion through a duodenal cannula. The vessel contractility was simultaneously quantified. We demonstrated for the first time that collecting lymphatic vessels respond to an acute lipid load by reducing pump function. High lipid levels decreased contraction frequency and amplitude. We also showed a strong tonic response through a reduction in the end-diast...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Kassis, T., Yarlagadda, S. C., Kohan, A. B., Tso, P., Breedveld, V., Dixon, J. B. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Prucalopride exerts neuroprotection in human enteric neurons
This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated wi...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Bianco, F., Bonora, E., Natarajan, D., Vargiolu, M., Thapar, N., Torresan, F., Giancola, F., Boschetti, E., Volta, U., Bazzoli, F., Mazzoni, M., Seri, M., Clavenzani, P., Stanghellini, V., Sternini, C., De Giorgio, R. Tags: RAPID REPORT Source Type: research

5-HT4-mediated neuroprotection: a new therapeutic modality on the way?
(Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: Gershon, M. D. Tags: EDITORIAL FOCUS Source Type: research

Lin28 and let-7: roles and regulation in liver diseases
The diagnosis and treatment of liver disease remain a major health concern worldwide because of the diverse etiologies of this disease. For this reason, new therapeutic targets are greatly needed to halt the progression of this damaging disease. Upon initiation of liver injury by viral infection, autoimmune disease or toxin, and/or hepatitis, chronic disease may develop, which can progress to cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma, liver failure, or death. The Lin28/lethal-7 (let-7) molecular switch has emerged as a central regulator of multiorgan injuries and cancer development. Lin28 is a stem cell...
Source: AJP: Gastrointestinal and Liver Physiology - May 14, 2016 Category: Gastroenterology Authors: McDaniel, K., Hall, C., Sato, K., Lairmore, T., Marzioni, M., Glaser, S., Meng, F., Alpini, G. Tags: REVIEW Source Type: research

Soluble guanylate cyclase activation during ischemic injury in mice protects against postischemic inflammation at the mitochondrial level
In conclusion, selective activation of oxidized sGC of WT and HO-1–/– during ischemia protects against I/R-induced inflammation and preserves mucosal integrity in part by reducing pCyPD production and mPTP formation. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - April 30, 2016 Category: Gastroenterology Authors: Wang, D. Z., Jones, A. W., Wang, W. Z., Wang, M., Korthuis, R. J. Tags: INFLAMMATION, IMMUNITY, AND INFECTION Source Type: research

VEGF-sdf1 recruitment of CXCR7+ bone marrow progenitors of liver sinusoidal endothelial cells promotes rat liver regeneration
In liver injury, recruitment of bone marrow (BM) progenitors of liver sinusoidal endothelial cells (sprocs) is necessary for normal liver regeneration. Hepatic vascular endothelial growth factor (VEGF) is a central regulator of the recruitment process. We examine whether stromal cell-derived factor 1 [sdf1, or CXC ligand 12 (CXCL12)] acts downstream from VEGF to mediate recruitment of BM sprocs, what the sdf1 receptor type [CXC receptor (CXCR)-4 or CXCR7] is on sprocs, and whether sdf1 signaling is required for normal liver regeneration. Studies were performed in the rat partial hepatectomy model. Tracking studies of BM sp...
Source: AJP: Gastrointestinal and Liver Physiology - April 30, 2016 Category: Gastroenterology Authors: DeLeve, L. D., Wang, X., Wang, L. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Liver-specific loss of Perilipin 2 alleviates diet-induced hepatic steatosis, inflammation, and fibrosis
Hepatic inflammation and fibrosis are key elements in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive liver disease initiated by excess hepatic lipid accumulation. Lipid droplet protein Perilipin 2 (Plin2) alleviates dietary-induced hepatic steatosis when globally ablated; however, its role in the progression of NASH remains unknown. To investigate this further, we challenged Plin2 liver-specific knockout mice (designated L-KO) and their respective wild-type (WT) controls with a methionine-choline-deficient (MCD) diet for 15 days to induce a NASH phenotype of increased hepatic triglyceride levels thr...
Source: AJP: Gastrointestinal and Liver Physiology - April 30, 2016 Category: Gastroenterology Authors: Najt, C. P., Senthivinayagam, S., Aljazi, M. B., Fader, K. A., Olenic, S. D., Brock, J. R. L., Lydic, T. A., Jones, A. D., Atshaves, B. P. Tags: LIVER AND BILIARY TRACT PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research