Abstract:
BACKGROUND & AIMS:Nonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis. METHODS:We collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis. RESULTS:Livers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice. CONCLUSIONS:In an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be used to monitor disease progression and identify therapeutic targets for patients.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Alonso C,Fernández-Ramos D,Varela-Rey M,Martínez-Arranz I,Navasa N,Van Liempd SM,Lavín Trueba JL,Mayo R,Ilisso CP,de Juan VG,Iruarrizaga-Lejarreta M,delaCruz-Villar L,Mincholé I,Robinson A,Crespo J,Martín-Duce A,Romero-Gódoi
10.1053/j.gastro.2017.01.015subject
Has Abstractpub_date
2017-05-01 00:00:00pages
1449-1461.e7issue
6eissn
0016-5085issn
1528-0012pii
S0016-5085(17)30072-0journal_volume
152pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract:BACKGROUND & AIMS:Transplantation of wild-type (H-2k) bone marrow into tg epsilon26 mice (BM-->tg epsilon26) induces colitis, characterized by T-helper cell type 1 activation in the lamina propria. Here we determined whether pathogenic T-cell clones could be derived by serial adoptive transfers into healthy tg epsilon2...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2005.01.060
更新日期:2005-05-01 00:00:00
abstract::The effect of experimental bypass on the intestinal epithelium of the rat was investigated from 2 to 360 days after creating a Thiry-Vella fistula. Within 7 to 14 days the number of cells per villus column and, to a lesser degree, the number of cells per crypt column decreased and subsequently these values remained co...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract:BACKGROUND & AIMS:Chronic hepatitis C virus (HCV) infection is a major burden on individuals and health care systems. The Extension for Community Healthcare Outcomes (Project ECHO) enables primary care providers to deliver best-practice care for complex conditions to underserved populations. The US Congress passed the ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2017.10.016
更新日期:2017-12-01 00:00:00
abstract::Among the components of dietary fiber, the soluble polysaccharides, primarily guaran and pectin, have been found to impair intestinal absorption. Little is known, however, about the mechanism of this effect. The direct action of guaran on small intestinal absorption was evaluated by a single-pass perfusion technique. ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND & AIMS:Ethanol impairs the mitochondrial transport of reduced glutathione (GSH), resulting in lower mitochondrial GSH (mGSH) levels. Our purpose was to evaluate the role of acetaldehyde on the regulation of mGSH in HepG2 cells. METHODS:mGSH levels and transport, mitochondrial membrane microviscosity, and li...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2003.50089
更新日期:2003-03-01 00:00:00
abstract::Sweden has one of the highest incidences of gallstone disease in the Western world. It is therefore important to characterize the mechanisms responsible for the formation of cholesterol gallstones in this population. In the present study, we have determined the kinetics of the two primary bile acids, cholic acid and c...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(85)90328-2
更新日期:1985-08-01 00:00:00
abstract:BACKGROUND & AIMS:There are intra- and interobserver variations in endoscopic assessment of ulcerative colitis (UC) and biopsies are often collected for histologic evaluation. We sought to develop a deep neural network system for consistent, objective, and real-time analysis of endoscopic images from patients with UC. ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2020.02.012
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND & AIMS:Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relations...
journal_title:Gastroenterology
pub_type: 杂志文章,meta分析
doi:10.1053/j.gastro.2018.06.040
更新日期:2018-10-01 00:00:00
abstract::To investigate the role of gastric inhibitory polypeptide (GIP), a potent inhibitor of gastric acid secretion, in the hypersecretion associated with duodenal ulcer, we compared the serum GIP concentrations in 11 healthy subjects and 16 duodenal ulcer patients after the stimulation of GIP release by a mixed meal. Fasti...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract:BACKGROUND & AIMS:Helicobacter pylori infection is mainly acquired in early childhood, but the exact routes of transmission remain elusive. To distinguish between risks of intrafamilial and extraneous child-to-child transmission, we studied H. pylori seroprevalence among Swedish school children with varying family back...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2001.26282
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND & AIMS:Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) w...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究
doi:10.1053/j.gastro.2018.08.036
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND & AIMS:Recently, the immediate early gene h-sgk was cloned as a hypertonicity-induced gene from human hepatoma cells. The aim of this study was to localize h-sgk messenger RNA (mRNA) expression in normal and inflamed intestinal mucosa and to identify potential transcriptional regulators. METHODS:h-sgk mRNA ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(99)70011-9
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND & AIMS:Ischemia and reperfusion injury are common causes of oxidative tissue damage associated with many liver diseases and hepatic surgery. The Wnt-β-catenin signaling pathway is an important regulator of hepatic development, regeneration, and carcinogenesis. However, the role of Wnt signaling in the hepato...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2011.04.051
更新日期:2011-08-01 00:00:00
abstract::Approximately 5% of the world's human population have an increased risk for developing liver cancer and cirrhosis as a direct consequence of chronic infection with the hepatitis B virus (HBV). Antiviral chemotherapy remains the only option for controlling infection in these individuals, for whom the current licensed h...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1016/s0016-5085(00)70008-4
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND & AIMS:Patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels have been routinely excluded from large randomized treatment trials; consequently, the efficacy and safety of antiviral therapy in this population are unknown. METHODS:Patients with at least 3 normal ALT v...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2004.09.050
更新日期:2004-12-01 00:00:00
abstract::This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute on "Use of Gastrointestinal Medications in Pregnancy." It was approved by the Clinical Practice and Economics Committee on February 22, 2006, and by the AGA Institute Governing Board on April 20, 2006. ...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2006.04.048
更新日期:2006-07-01 00:00:00
abstract::The effect of secretin5-27 and four substituted analogues (9 Gln-secretin5-27, 15-Asn-secretin5-27, 9-Gln-15-Asn-secretin5-27, and 15-Lys-secretin5-27) on pancreatic secretion in the rat and guinea pig was examined. Secretin5-27 retained significant pancreatic secretory activity in both species. Its efficacy (intrinsi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1978-08-01 00:00:00
abstract:BACKGROUND & AIMS:Parenteral methotrexate is an effective treatment for patients with Crohn's disease, but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC. METHODS:We perf...
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.2015.10.050
更新日期:2016-02-01 00:00:00
abstract:BACKGROUND:It was recently reported that ventromedial hypothalamic (VMH) lesions produced an increase in gastrointestinal DNA content in rats. In the present study, the mechanism of this alteration was examined. METHODS:The DNA content and synthesis after VMH lesioning in rat gastrointestinal tracts were determined. ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(93)90416-a
更新日期:1993-02-01 00:00:00
abstract:BACKGROUND & AIMS:Although a significant amount of regenerating gene (REG) Ialpha protein is present not only in normal gastric mucosa but also in gastric cancer tissues, its pathophysiologic role in gastric cancer development remains unclear. We investigated REG Ialpha protein expression in early gastric cancers, and ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2004.12.045
更新日期:2005-03-01 00:00:00
abstract::Frequent occurrence of post-transfusion hepatitis continues despite screening for Australia antigen in blood before transfusion and elimination of commercial donor sources. The majority of these cases appears unrelated to hepatitis B virus. Preoperative, acute, and convalescent serra were screened for evidence of hepa...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::Insulinlike growth factor I is a potent mitogen with insulinlike metabolic effects. Insulinlike growth factor I is synthesized in the liver, intestine, and other organs. Insulinlike growth factor I receptors are widely distributed and structurally similar to insulin receptors. Frozen sections of rabbit gastrointestina...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(90)91228-x
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND & AIMS:Gastritis is associated with development of stomach cancer, but little is known about changes in microRNA expression patterns during gastric inflammation. Specific changes in gene expression in epithelial cells are difficult to monitor because of the heterogeneity of the tissue. We investigated epithe...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2018.11.059
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND/AIMS:Gastrointestinal peptides and biogenic monoamines participate in the regulation of gastrointestinal functions. The aim of this study was to examine the influence of the microflora on the distribution of endocrine cells and on the release of gastrointestinal peptides. METHODS:A quantitative morphologica...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(94)90526-6
更新日期:1994-11-01 00:00:00
abstract::The influence of ethinyl estradiol (EE) on the effects of dietary cholesterol on the biliary saturation index and on the rate-limiting hepatic enzymes of cholesterol synthesis, hydroxymethylglutaryl-CoA-reductase, and bile acid synthesis, 7 alpha-hydroxylase, were determined. Four groups of 12 male hamsters were treat...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1978-07-01 00:00:00
abstract:BACKGROUND & AIMS:Polymorphisms in the region of the interleukin (IL)-28B gene on chromosome 19 have been associated with peginterferon-alfa-induced clearance of genotype 1 hepatitis C virus (HCV); there are no data for patients with genotype 2 or 3 HCV. We evaluated the effects of IL-28B polymorphisms on response to t...
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.2010.05.079
更新日期:2010-09-01 00:00:00
abstract::Heterogeneity of colonic mucin glycoprotein was examined in rectal mucosal biopsy specimens from a variety of primate species (Saguinus oedipus, n = 18; Macaca mulatta, n = 2; Macaca fascicularis, n = 2; Aotus trivirgatus, n = 2; Saimiri sciureus, n = 2; and Callithrix jacchus, n = 2). After initial separation of radi...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(85)80127-x
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND & AIMS:We have previously shown that patients with irritable bowel syndrome (IBS) have impaired transit of intestinal gas loads. Because abnormal gas retention can be experimentally reproduced in healthy subjects by pharmacological inhibition of gut motility, we hypothesized that impaired gas transit and ret...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1053/gast.2002.33658
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND & AIMS:Rabs are monomeric guanosine triphosphatases that regulate membrane trafficking and acid secretion in gastric parietal cells. Using a proteomics approach, we identified a new Rab, Rab27b, in tubulovesicle membranes and determined its role in parietal cell activation. METHODS:We used mass spectrometry...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2010.09.044
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND & AIMS:Although dextran sodium sulfate (DSS)-induced colitis is a commonly used model of colonic injury, the mechanism of this model is not understood. The aim of this study was to determine the contribution of prostaglandins to the mechanism of DSS-induced epithelial injury. METHODS:Mice were treated with ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(98)70259-8
更新日期:1998-10-01 00:00:00