Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Microarray analysis of surgical liver biopsies from 13 obese (nine with type 2 diabetes) and five control subjects

ABSTRACT: Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays. Human liver samples were obtained from 5 lean control subjects undergoing elective cholecystectomy and 13 obese subjects (with or without Type 2 diabetes) undergoing gastric bypass surgery. Subjects with diabetes were classified as either well-controlled or poorly-controlled.

ORGANISM(S): Homo sapiens

SUBMITTER: Mary Elizabeth Patti

PROVIDER: E-GEOD-15653 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Thyroid hormone-related regulation of gene expression in human fatty liver.

Pihlajamäki Jussi J Boes Tanner T Kim Eun-Young EY Dearie Farrell F Kim Brian W BW Schroeder Joshua J Mun Edward E Nasser Imad I Park Peter J PJ Bianco Antonio C AC Goldfine Allison B AB Patti Mary Elizabeth ME

The Journal of clinical endocrinology and metabolism 20090623 9

<h4>Context</h4>Fatty liver is an important complication of obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified.<h4>Objective</h4>The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis.<h4>Design</h4>We evaluated gene expression in surgical liver biopsies from 13 obese (nine with ...[more]

PMID: 19549744

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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.

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.

Dataset Information

Microarray analysis of surgical liver biopsies from 13 obese (nine with type 2 diabetes) and five control subjects

Publications

Thyroid hormone-related regulation of gene expression in human fatty liver.

Similar Datasets

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