Transcriptomic study of human liver biopsies in obese patients with low and high liver fat
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Matej Oresic
PROVIDER: E-MTAB-4231 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Non-alcoholic fatty liver disease (NAFLD) is a major public health burden and it covers a spectrum of diseases. NAFLD starts with the accumulation of lipid droplets (LDs) within hepatocytes (steatosis). Part of the challenge of studying the mechanistic processes involved in LD accumulation and their implications on the pathogenesis of human NAFLD is due to the available models. Investigating hepatic LDs in humans is challenging and relies on liver biopsies, meaning only cross-sectional data be obtained. On the other hand, LD patterns in in vitro models are poorly defined and rarely reported. Diacylgylcerol acyltransferase (DGAT)2 is one of two enzymes that carry out the final committed step in triacylglycerol (TAG) synthesis. It is unclear whether the enzymes are able to compensate for each other or whether they have distinct roles. It has been hypothesised that DGAT1 primarily utilises exogenous fatty acids and DGAT2 uses de novo-derived fatty acids. Given the important role of this enzyme in TAG synthesis and accumulation, the aims of this study are first to create a cellular model of intrahepatocellular TAG accumulation by manipulating nutritional substrates and to investigate intracellular metabolism in wildtype and DGAT2 knockout cells under these conditions. The experimental workflow for this study is as follows: Huh7 cells (either wild type or knockout) were grown in media containing 11 mM glucose and 2% human serum (HS) for seven days before additional sugars and fatty acids (FAs) were added for a further seven days. All treatments contained 11 mM glucose and 2% HS, either with 200 µM FAs (low fat low sugar; LFLS), 5.5 mM fructose + 200 µM FAs (low fat high sugar; LFHS) or 5.5 mM fructose + 800 µM FAs (high fat high sugar; HFHS). FA metabolism, lipid droplet characteristics and transcriptomic signatures were investigated.
2020-08-21 | E-MTAB-7884 | biostudies-arrayexpress
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most prevalent hepatic pathology worldwide. However, the precise molecular mechanisms for NAFLD are still not sufficiently explained. Recently, a new mode of cell death (cuproptosis) is found. However, the relationship between NAFLD and cuproptosis remains unclear. We analyzed three public datasets to identify cuproptosis-related genes stably expressed in NAFLD. Then, we performed a series of bioinformatics analyses to explore the relationship between NAFLD and cuproptosis-related genes. Finally, 3 normal control mouse and 3 high-fat diet (HFD)-induced NAFLD C57BL/6J mouse models were established to carry out transcriptome analysis.
2023-04-30 | E-MTAB-11980 | biostudies-arrayexpress
Project description:In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. The complete database comprised the expression measurements of 48766 probes in liver biopsies. The liver biopsy specimens available for the study were obtained: a) before immunosuppressive drugs were discontinued from tolerant (TOL, n=24) and non-tolerant (Non-TOL, n=29) recipients; b) at the time of rejection from non-tolerant recipients (Non TOL REJ, n=18); In addition, liver tissue samples were also collected from the following control patient groups: a) liver transplant recipients with chronic hepatitis due to recurrent hepatitis C virus infection (HEPC, n=12); b) liver transplant recipients with typical acute cellular rejection taking place during the immediate post-transplant period (REJ, n=9); c) liver transplant recipients under maintenance immunosuppression with normal liver function and normal liver histology 1 year after transplantation (CONT-Tx, n=8); and d) non-transplanted patients undergoing surgery for colorectal liver metastases (CONT, n=10).
2012-01-09 | E-GEOD-26625 | biostudies-arrayexpress
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 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.
2015-07-02 | E-GEOD-59045 | biostudies-arrayexpress
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.
2015-08-04 | E-GEOD-58979 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE26622: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Affymetrix) GSE26625: MOLECULAR CHARACTERIZATION OF LIVER ALLOGRAFTS FROM OPERATIONALLY TOLERANT TRANSPLANT RECIPIENTS (Illumina) Refer to individual Series
2012-01-09 | E-GEOD-26627 | biostudies-arrayexpress
Project description:We have employed whole microRNA microarray with the potential to distinguish H.pylori infection.Among the 470 human miRNAs represented on the array chip, 228 were undetectable or expressed below the background and so were eliminated, leaving 242 miRNAs for the supervised analysis. When comparing 10 H. pylori-negative and nine H. pylori-positive subjects, 55 miRNAs were deemed significantly different on the basis of microRNA arrays. During endoscopy, a biopsy specimen was obtained from the gastric antrum along the lesser curvature. Biopsies of 10 H. pylori-negative and nine H. pylori-positive patients' subjects were performed.Exclusion criteria were: age <18 or >80 y, pregnancy, body mass index (BMI) >30 kg/m2, diabetes mellitus, cachectic state (including cancer), systemic infection, liver disease, renal impairment, use of medications effective against H. pylori during the preceding 3 months, alcohol abuse, drug addiction, and chronic corticosteroid or nonsteroidal anti-inflammatory drug use. None of the subjects had undergone gastrointestinal surgery.
2010-05-16 | E-GEOD-19769 | biostudies-arrayexpress
Project description:The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function, we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease. Microarray is one of these platforms. In this part, adult human liver tissues from 10 adult human were surgically resected due to hemangioma in the liver. The gene expression of normal human liver was detected by Microarray platform. The samples were obtained from the portion unaffected by the hemangioma and were immediately frozen in liquid nitrogen. All procedures and risks were explained verbally, and patients provided written consent. The samples were sectioned and confirmed to be histologically normal. All laboratory data assessing hepatic function were within normal ranges, including serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin, albumin, prothrombin activity, glucose, cholesterol, and triglycerides (data not shown). Serological tests for hepatitis B surface antigen, hepatitis C virus antibodies, and human immunodeficiency virus antibodies also proved negative. Neither heavy alcohol consumption nor the intake of prescription or other drugs was observed before surgical resection. Total RNA was extracted according to the manufacturer’s instructions, and RNase-free DNase I was used to remove DNA contamination. Nucleic acid concentration and purity were assessed at 260 nm using a spectrophotometer (DU 530, Beckman-Coulter Inc., Fullerton, CA), and the quality was assessed using an Agilent 2100 Bioanalyzer. In order to address gene expression polymorphism, the total RNA from 10 livers was pooled. ***This submission represents the Affymetrix component of the study only***
2010-09-18 | E-GEOD-24042 | biostudies-arrayexpress
Project description:Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARalpha challenge demonstrated the dysregulation of PPARalpha signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21â??s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver. Male C57Bl/6J mice were divided to 3 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR) and medium fat (MF; AIN-93W-MF; 25% energy from fat). Dietary interventions started at the age of 9 weeks and sacrifice was performed at the age of 6, 12, 24 and 28 months. We performed various measurements on metabolic parameters and gene expression analysis. This entry represents the microarray data.
2016-08-09 | E-GEOD-84495 | biostudies-arrayexpress
Project description:Aberrant gene expression between HCC tumor tissues, histologically normal adjacent liver tissues and peripheral blood mononuclear cell (PBMC) samples from healthy individuals and patients with pancreatic carcinoma, gastric carcinoma and HCC were identified using Affymetrix gene arrays. A 13-member HCC-specific gene signature was identified and validated via custom-designed quantitative multiplexed gene expression analysis using the GenomeLab GeXP Genetic Analysis System (GeXP). Peripheral blood mononuclear cell (PBMC) from healthy individuals, patients with pancreatic carcinoma, gastric carcinoma, and HCC were isolated and total RNA was extracted for Affymetrix gene microarray analysis.
2014-02-24 | E-GEOD-36076 | biostudies-arrayexpress