Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression in liver of morbidly obese patients

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease affecting 20-30% of the population in developed countries. NAFLD is strongly associated with abdominal obesity and is recognized as the hepatic manifestation of the metabolic syndrome. In a subgroup of patients with NAFLD inflammation and fibrosis develops, this so-called Non-Alcoholic Steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. A multi-hit hypothesis has been proposed in which during the first “hit” fat accumulation occurs in hepatocytes from excessive delivery of fatty acids from adipose tissue, in addition there is an imbalance in lipid synthesis and export. However, the reason why fat accumulation is subsequently followed by inflammation and fibrosis in some patients is poorly understood. We studied the role of gene expression at the transcriptional level using microarray in bariatric patients from whom the liver histology was available. Patients scheduled for bariatric surgery were recruited in Pretoria/South-Africa. At the time of the procedure, tissue samples of the visceral and subcutaneous fat were taken for molecular analysis as well as liver tissue for histology, also full biochemical data was collected. Patients were grouped according histology: group I (<5% steatosis), group II (NAFLD, 30-50% steatosis) and group III (NASH). The 15 samples were used for microarray (nr patients respectively for stages I-II-III: 6-4-5).This dataset is part of the TransQST collection.

ORGANISM(S): Homo sapiens

SUBMITTER: Wouter Van Delm

PROVIDER: E-GEOD-59045 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Association of Adipose Tissue Inflammation With Histologic Severity of Nonalcoholic Fatty Liver Disease.

du Plessis Johannie J van Pelt Jos J Korf Hannelie H Mathieu Chantal C van der Schueren Bart B Lannoo Matthias M Oyen Tom T Topal Baki B Fetter Gary G Nayler Simon S van der Merwe Tessa T Windmolders Petra P Van Gaal Luc L Verrijken An A Hubens Guy G Gericke Martin M Cassiman David D Francque Sven S Nevens Frederik F van der Merwe Schalk S

Gastroenterology 20150528 3

<h4>Background & aims</h4>The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the obesity pandemic. We analyzed the transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), and phenotypes and functional characteristics of adipocyte tissue macrophages (ATMs), in obese patients undergoing bariatric surgery.<h4>Methods</h4>We collected anthropometric data; plasma samples; and SAT, VAT, and liver tissues from 113 obese patients underg ...[more]

PMID: 26028579

Similar Datasets

Project description:Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of liver disease affecting 20-30% of the population in developed countries. NAFLD is strongly associated with abdominal obesity and is recognized as the hepatic manifestation of the metabolic syndrome. In a subgroup of patients with NAFLD inflammation and fibrosis develops, this so-called Non-Alcoholic Steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. A multi-hit hypothesis has been proposed in which during the first “hit” fat accumulation occurs in hepatocytes from excessive delivery of fatty acids from adipose tissue, in addition there is an imbalance in lipid synthesis and export. However, the reason why fat accumulation is subsequently followed by inflammation and fibrosis in some patients is poorly understood. We studied the role of inflammatory processes in visceral and subcutaneous fat at the transcriptional level using microarray in bariatric patients from whom the liver histology was available. Patients scheduled for bariatric surgery were recruited in two centers (Pretoria/South-Africa and Antwerpen/Belgium). At the time of the procedure, tissue samples of the visceral and subcutaneous fat were taken for molecular analysis as well as liver tissue for histology, also full biochemical data was collected. Patients were grouped according histology: group I (<5% steatosis), group II (NAFLD, 30-50% steatosis), group III (NASH) and group IV (NASH + fibrosis F2-F3). The following samples were used for microarray (number of 'patients' respectively for stages I-II-III-IV): visceral fat (9-7-7-5), subcutaneous fat (6-6-6-5). Microarrays were run in two batches (15xxx versus 17xxx CEL file samples; indicated in the description field). Samples from two patients (FN61; FN76) were put twice on array (15078+17881; 15064+17877) to verify and exclude batch effects. Please note that, due to technical repeats with two patient samples, the number of 'visceral fat samples' for stages I-II-III-IV is 10-7-8-5.

Project description:Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH. Keywords: Expression profiling by array Male wildtype C57Bl/6 mice were fed LFD or HFD for 21 weeks. Mice were divided into 4 groups based on liver histology.

Project description:Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of histological findings, from simple steatosis to steatohepatitis (NASH), the latter presenting a higher risk of cardiovascular and kidney diseases, type 2 diabetes and end-stage liver disease. NAFLD is seen as the hepatic manifestation of the metabolic syndrome and affects up to 70-80% of obese patients. There are currently no approved pharmacological therapies for NASH, thus the only option is lifestyle intervention or bariatric surgery in order to lose weight and to improve insulin resistance. Although surgical intervention has allowed collections of liver biopsies, transcriptomic data from livers are still scarce and especially follow-up data to evaluate the impact of weight loss intervention on the liver. Therefore we studied hepatic transcriptomic data in a large cohort of obese patients assessed for presence of NASH at baseline and 1 year follow-up. Patients visiting the obesity clinic of the Antwerp University Hospital for a problem of being overweight (BMI above 25 to 29.9 kg/m²) or obese (BMI above 30 kg/m²) were prospectively recruited and underwent a hepatic work-up. Patients were excluded from further analysis in case of significant alcohol consumption (>20 g/day), history of bariatric surgery, diagnosis of another liver disease, pre-existing diabetes. Patients who were, however, diagnosed with de novo diabetes at baseline or at follow-up were not excluded. If NAFLD was suspected, liver biopsy was proposed. For patients undergoing bariatric surgery (BS), a liver biopsy was proposed regardless of the criteria. Patients were reassessed after 1 year. Liver biopsy was performed percutaneously (16G Menghini) or peri-operatively (14G Tru-Cut). The different histological features of NAFLD were assessed using the NASH Clinical Research Network (NASH CRN) Scoring System. The presence of NASH was defined according to Chalasani et al. necessitating the combined presence of steatosis, ballooning and lobular inflammation.

Project description:Background & Aims: Bariatric surgery is associated with improved outcomes in subjects with severe obesity. We aimed to determine the prognostic relevance of liver histology in a large cohort of obese patients undergoing bariatric surgery. Methods: In a single center cohort of 492 subjects undergoing Roux-en-Y gastric bypass bariatric surgery with routine perioperative liver biopsy at Geneva University Hospital between January 1997 to December 2004, clinical and histopathological variables were analyzed for association with overall survival. Survival of the cohort was compared to age- and sex-matched life tables from the Swiss general population and propensity score-matched subjects from the third National Health and Nutrition Examination Survey (NHANES III). A 32-gene signature was evaluated in the liver tissue of 47 non-alcoholic steatohepatitis (NASH) subjects. Results: Median body mass index was 43.6 kg/m2. Twenty-one patients (4.2%) died during a median follow-up of 10.3 years. At baseline liver histology, 12% and 16% of subjects had NASH, and fibrosis, respectively. In multivariable Cox regression, presence of NASH (hazard ratio [HR] 3.4, p=0.0087), age greater than 50 years (HR 2.7, p=0.044), hypertension (HR 3.8, p=0.021), and short-term postoperative complications (HR 2.8, p=0.048) were associated with overall survival. Compared to matched NHANES III subjects, bariatric surgery improved long-term survival (HR 0.54, p=0.035), although this benefit was not observed in the subgroup of NASH patients (HR 0.97, p=0.94). A 32-gene poor prognosis signature prediction was associated with worse overall survival within NASH subjects (n=47, HR = 7.7, p=0.03 ). Conclusions Histologically proven NASH was associated with increased long-term mortality in subjects undergoing bariatric surgery. Although survival benefit of bariatric surgery may be limited in obese patients with NASH, a 32-gene expression signature appears to predict long term mortality in these patients.

Dataset Information

Gene expression in liver of morbidly obese patients

Publications

Association of Adipose Tissue Inflammation With Histologic Severity of Nonalcoholic Fatty Liver Disease.

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