Abstract:
BACKGROUND & AIMS:A high-fat diet (HFD) can cause serious health problems, including alteration of gastrointestinal transit, the exact mechanism of which is not clear. Several microRNAs (miRNAs) are involved in energy homeostasis, lipid metabolism, and HFD-induced weight gain. We investigated the role of miRNAs in HFD-induced damage to the enteric nervous system. METHODS:Male mice were fed a HFD (60% calories from fat) or regular diets (18% calories from fat) for 11 weeks. Mice on regular diets and HFDs were given intraperitoneal injections of Mir375 inhibitor or a negative control. Body weights, food intake, stool indices, and gastrointestinal transit (following Evans blue gavage) were measured. An enteric neuronal cell line (immorto-fetal enteric neuronal) and primary enteric neurons were used for in vitro studies. RESULTS:HFD delayed intestinal transit, which was associated with increased apoptosis and loss of colonic myenteric neurons. Mice fed a low-palmitate HFD did not develop a similar phenotype. Palmitate caused apoptosis of enteric neuronal cells associated with mitochondrial dysfunction and endoplasmic reticulum stress. Palmitate significantly increased the expression of Mir375 in vitro; transfection of cells with a Mir375 inhibitor prevented the palmitate-induced enteric neuronal cell apoptosis. Mir375 expression was increased in myenteric ganglia of mice fed HFD and associated with decreased levels of Mir375 target messenger RNAs, including Pdk1. Systemic injection of a Mir375 inhibitor for 5 weeks prevented HFD-induced delay in intestinal transit and morphologic changes. CONCLUSIONS:HFDs delay colonic transit, partly by inducing apoptosis in enteric neuronal cells. This effect is mediated by Mir375 and is associated with reduced levels of Pdk1. Mir375 might be targeted to increase survival of enteric neurons and gastrointestinal motility.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Nezami BG,Mwangi SM,Lee JE,Jeppsson S,Anitha M,Yarandi SS,Farris AB 3rd,Srinivasan Sdoi
10.1053/j.gastro.2013.10.053subject
Has Abstractpub_date
2014-02-01 00:00:00pages
473-83.e3issue
2eissn
0016-5085issn
1528-0012pii
S0016-5085(13)01527-8journal_volume
146pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract:BACKGROUND & AIMS:The evaluation of patients with chronic watery diarrhea represents a diagnostic challenge for clinicians because organic causes, including inflammatory bowel disease, microscopic colitis, and chronic infection, must be differentiated from functional diarrhea and diarrhea-predominant irritable bowel sy...
journal_title:Gastroenterology
pub_type: 杂志文章,实务指引,评审
doi:10.1053/j.gastro.2019.06.014
更新日期:2019-09-01 00:00:00
abstract::The effect of substance P (SP) on the release of gastric somatostatinlike immunoreactivity (SLI) was studied. Substance P inhibited both basal SLI release and SLI release stimulated by gastric inhibitory polypeptide or 1-isoproterenol. This inhibitory action of SP was not blocked by atropine or hexamethonium, suggesti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(85)80138-4
更新日期:1985-01-01 00:00:00
abstract::Gastrinomas were localized by concurrent blood sampling in the hepatic vein and portal vein tributaries in 10 of 12 Zollinger-Ellison patients. In one patient, the portal vein could not be catheterized; in the other, a gastrin gradient could not be picked up in either of two examinations. Six of the patients were subs...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::The effects of pancreatic duct ligation on the digestion and absorption of a randomly 14C-labeled protein meal has been investigated in the rat. Although there was a significant reduction in luminal digestion and absorption of the protein meal in the pancreatic duct-ligated animals compared with controls, 37% of admin...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::We have conducted a double-blind controlled trial of colchicine in patients with primary biliary cirrhosis. Fifty-seven patients with biopsy-proven primary biliary cirrhosis were randomized to receive either 0.6 mg of colchicine twice daily or an identically appearing placebo. Patients underwent clinical and laborator...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0016-5085(88)90300-9
更新日期:1988-07-01 00:00:00
abstract::This study was performed to ascertain whether testosterone metabolism is altered in male rats with portal bypass, and whether such changes could contribute to the reduction in serum testosterone concentration and raised serum estrogen levels that are observed in this situation. The metabolic clearance rate of testoste...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90500-8
更新日期:1988-08-01 00:00:00
abstract::It has been suggested that the lower esophageal sphincter (LES) plays an important role in preventing gastroesophageal reflux. This study was designed to determine if abolition of the LES alone is sufficient to induce gastroesophageal reflux and esophagitis. Studies were performed in the Australian brush-tailed possum...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-09-01 00:00:00
abstract:BACKGROUND & AIMS:The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a transmembrane glycoprotein with pleotropic functions, including clearance of hepatic insulin. We investigated the functions of the related protein CEACAM2, which has tissue-specific distribution (kidney, uterus, and crypt epi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2010.03.056
更新日期:2010-08-01 00:00:00
abstract::Low residue, chemically defined diets containing all essential nutrients in a readily assimilated form, require minimal digestion and are almost entirely absorbed in the upper gastrointestinal tract. Within the past decade, these diets have been reported to provide nutritional support in a variety of clinical situatio...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:
更新日期:1975-12-01 00:00:00
abstract::The human gastrointestinal tract contains distinct microbial communities that differ in composition and function based on their location, as well as age, sex, race/ethnicity, and diet of their host. We describe the bacterial taxa present in different locations of the GI tract, and their specific metabolic features. Th...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2014.01.052
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND & AIMS:Despite high morbidity and mortality of alcoholic liver disease worldwide, the molecular mechanisms underlying alcohol-induced liver cell death are not fully understood. Transglutaminase 2 (TG2) is a cross-linking enzyme implicated in apoptosis. TG2 levels and activity are increased in association wit...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.01.007
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND & AIMS:Reactive oxidative species (ROS) are believed to be involved in the progression of nonalcoholic steatohepatitis (NASH). However, little is known about the sources of ROS in hepatocytes or their role in disease progression. We studied the effects of nicotinamide adenine dinucleotide phosphate reduced o...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2015.04.009
更新日期:2015-08-01 00:00:00
abstract::The hemodynamic effects of octreotide were studied in 20 patients with hepatitis B-related cirrhosis. In patients receiving a 100-micrograms bolus and a 100-micrograms/h infusion, heart rate, cardiac index, and systemic vascular resistance showed no significant changes, whereas right atrial pressure, pulmonary capilla...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(92)91117-m
更新日期:1992-07-01 00:00:00
abstract:BACKGROUND & AIMS:Gastroenteropancreatic neuroendocrine cells secrete chemical messengers in a calcium-dependent fashion. So far, other second messenger systems involved in regulated secretion have gained little attention. The aim of this study was to characterize guanosine 3',5'-cyclic monophosphate (cGMP)-mediated ve...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(98)70593-1
更新日期:1998-04-01 00:00:00
abstract::The existence of high- and low-affinity cholecystokinin (CCK)-A receptors on rodent pancreatic acini is well established. Until recently, CCK was believed to act directly on pancreatic acini to stimulate pancreatic secretion in both rodents and humans. However, conclusive evidence that human pancreatic acini lack func...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2004.05.002
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND AND AIMS:Diffuse-type gastric cancer (GC) is currently subdivided into signet-ring cell carcinoma (SRCC) and non-SRCC, referred to as poorly cohesive carcinoma not otherwise specified (PCC-NOS). Although these subtypes are considered to be independent, they often coexist in the same tumors, raising a questio...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2020.10.047
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND & AIMS:Small intestinal carcinomas are rare but occur with increased incidence in Crohn's disease. The aim of this study was to elucidate the genetic alterations. METHODS:Mutations and deletions involved in colorectal carcinoma were studied in sporadic and Crohn's-associated intestinal carcinomas and precur...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(97)70087-8
更新日期:1997-07-01 00:00:00
abstract::Methylbenzylnitrosamine is an esophageal-specific carcinogen in the rat, and the incidence of methylbenzylnitrosamine-induced esophageal carcinoma is increased by dietary zinc deficiency. Methylbenzylnitrosamine requires activation by cytochrome P-450 to be mutagenic; the present study examined the role of dietary zin...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(92)90009-n
更新日期:1992-09-01 00:00:00
abstract::A randomized, double-blind comparison of lactose enemas plus placebo tablets vs. starch enemas plus neomycin tablets was performed on 18 patients with acute portal systemic encephalopathy. Ten patients received starch enemas (10%; 1000 ml t.i.d.) plus neomycin tablets and 8 patients received lactose enemas (20%; 1000 ...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1981-07-01 00:00:00
abstract:BACKGROUND & AIMS:Modulation of the host innate immune response is an attractive means of inhibiting hepatitis C virus (HCV) replication. Having previously determined that expression of the interferon-sensitive gene (ISG)15 protease USP18 is increased in the liver biopsy specimens of patients who do not respond to inte...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2006.08.043
更新日期:2006-11-01 00:00:00
abstract::Four Puerto Rican sisters had recurrent prolonged cholestasis of pregnancy without preexisting or intercurrent hepatic disorders. Available information was reviewed on the course, mechanism, and sequelae of prolonged recurrent cholestasis after 14 pregnancies in the 4 sisters. Etiologic, clinical, laboratory, radiolog...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(97)70193-8
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND & AIMS:Patients affected by familial adenomatous polyposis (FAP) are at increased risk of developing duodenal adenomas. In this study, cell proliferation of duodenal mucosa was analyzed to detect kinetic abnormalities related to cancer risk. METHODS:Duodenal biopsy specimens were collected in three groups o...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.1997.v113.pm9322510
更新日期:1997-10-01 00:00:00
abstract::Fetal bile salt metabolism was assessed by the intravenous infusion of e114C]cholate into 6 monkey fetuses. The placental transfer, fetal plasma clearance, and fetal hepatic excretion of the administered radiolabeled bile salt were measured. Placental transfer averaged 30% of the injected dose, while biliary excretion...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract:BACKGROUND:The epidemiology of anorectal melanoma has not been well studied despite its potential relevance to the cutaneous melanoma epidemic, and prognostic studies have generally been based on referred cases. METHODS:Data reported to nine population-based registries in the United States during 1973 through 1987 wer...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(93)90849-8
更新日期:1993-01-01 00:00:00
abstract::In vitro studies have shown that some bile salts inhibit the growth of intestinal bacteria. We investigated the possibility that bile salts might have a similar action in vivo in the ileum by performing serial anaerobic cultures and bile salt analyses on postprandial ileal fluid obtained anaerobically via intestinal t...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-08-01 00:00:00
abstract::Chronic liver diseases (CLDs), due to chronic hepatitis C; hepatitis B; nonalcoholic fatty liver diseases (NAFLD); and alcoholic liver disease, are a leading cause of morbidity and mortality globally. Early identification of patients with cirrhosis at high risk of progression to liver-related complications may facilit...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2017.03.016
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND & AIMS:Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are potent antiviral agents that might have additive or synergistic antiviral activity in treatment of patients with chronic hepatitis B (CHB). We compared the efficacy and safety of ETV monotherapy with those of a combination of ETV and TDF. ME...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2012.05.037
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND & AIMS:The parietal cell has secretory receptors for histamine and acetylcholine, whereas the functional nature of the gastrin/cholecystokinin B receptor is controversial. This study in isolated gastric glands investigates the cholecystokinin B receptor-induced intracellular calcium concentration ([Ca]i) res...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(95)90563-4
更新日期:1995-10-01 00:00:00
abstract:BACKGROUND & AIMS:SMAD4 frequently is lost from colorectal cancers (CRCs), which is associated with the development of metastases and a poor prognosis. SMAD4 loss is believed to alter transforming growth factor β signaling to promote tumor progression. However, SMAD4 is also a central component of the bone morphogeneti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2014.03.052
更新日期:2014-07-01 00:00:00
abstract::Sixty-six outpatients with active ulcerative colitis who were intolerant of sulfasalazine were treated in a double-blind randomized trial. They received placebo or olsalazine sodium in daily doses of 0.75, 1.5, or 3 g. Overall, 35% of patients receiving olsalazine improved clinically, compared to 16% of patients recei...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0016-5085(87)90253-8
更新日期:1987-12-01 00:00:00