Hepatic senescence is associated with clinical progression of NAFLD/NASH: Role of BMP4 and its antagonist Gremlin1 (Visceral adipose cells)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200678 | GEO | 2022/06/29
REPOSITORIES: GEO
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Project description:Hepatic senescence is associated with clinical progression of NAFLD/NASH: Role of BMP4 and its antagonist Gremlin1 (Visceral adipose cells)
| PRJNA825838 | ENA
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:Non-alcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that can progress from simple fatty liver disease to non-alcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism and excretion (ADME) of drugs. Differential gene expression between three clinically defined pathological groups; normal, steatosis and NASH was analyzed. The samples were diagnosed as normal, steatotic, NASH with fatty liver (NASH fatty) and NASH without fatty liver (NASH NF). Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChipM-. Human 1.0ST arrays
2011-07-12 | E-MEXP-3291 | biostudies-arrayexpress
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s. A total of 4 wild-type mice were administered a standard diet (STD; control group) and 4 wild-type mice were administered a HFHC diet (HFHC).
2014-01-03 | E-GEOD-53381 | biostudies-arrayexpress
Project description:Obesity is associated with insulin resistance, an important risk factor of type 2 diabetes, atherogenic dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and cardiovascular disease. It has been postulated that accumulation of visceral adipose tissue (VAT) causes obesity-induced insulin resistance. The major purpose of this study was to test hypothesis that prophylactic VAT removal prevents the development of obesity-induced multi-organ (liver, skeletal muscle, adipose tissue) insulin resistance, dyslipidemia, and NAFLD. Accordingly, we surgically removed epididymal VAT from adult C57BL/6J mice and then evaluated in vivo and cellular metabolic pathways involved in glucose and lipid metabolism following feeding of chronic high-fat diet (HFD). We found that VAT removal prevented HFD-induced insulin resistance and markedly increased AKT-mediated insulin signaling in subcutaneous adipose tissue (SAT), liver, and skeletal muscle. VAT removal improved plasma lipid profiling and prevented obesity-induced NAFLD. In addition, VAT removal significantly increased circulating level of adiponectin, a key insulin-sensitizing adipokine, whereas it decreased interleukin-6, a pro-inflammatory adipokine. Data obtained from RNA-sequencing suggest that VAT removal prevents obesity-induced oxidative stress and inflammation in liver and SAT respectively. These findings demonstrate the causative role of VAT in the development of obesity and related systemic metabolic complications, such as insulin resistance, dyslipidemia, and NAFLD.
2021-04-01 | GSE157798 | GEO
Project description:Non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) is a significant risk factor for hepatocellular carcinoma (HCC). However, a preclinical model of progressive NAFLD/NASH is largely lacking. Here, we report that mice with hepatocyte-specific deletion of Tid1, encoding a mitochondrial cochaperone, tended to develop NASH-dependent HCC. Mice with hepatic Tid1 deficiency showed impairing mitochondrial function and causing fatty acid metabolic dysregulation; meanwhile, sequentially developed fatty liver, NASH, and cirrhosis/HCC in a diethylnitrosamine (DEN) induced oxidative environment. The pathological signatures of human NASH, including cholesterol accumulation and activation of inflammatory and apoptotic signaling pathways, are also present in these mice. Clinically, low Tid1 expression was associated with unfavorable prognosis in patients with HCC. Empirically, hepatic Tid1 deficiency directly disrupts entire mitochondria that play a key role in the NASH-dependent HCC development. Overall, we established a new mouse model that develops NASH-dependent HCC and provides a promising approach to improve the treatment.
2022-06-02 | E-MTAB-9973 | biostudies-arrayexpress
Project description:We investigated the hepatic transcriptome of 58 biopsy-proven NAFLD patients at multiple stages of the disease (NAFL, NASH with mild fibrosis, NASH with advanced fibrosis) with the aim of describing the pathophysiological events driving the development and progression of NASH.
2021-04-14 | E-MTAB-9815 | biostudies-arrayexpress
Project description:To investigate the mechanism of hepatic Activin A and Gpnmb in NAFLD/NASH, we studied C57BL/6J mice on a FPC NASH diet and sugar water for 16 weeks, compared with standard chow diet, and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control), or AAV8-H1-shRNA to knockdown of Gpnmb or scramble control in NAFLD/NASH liver. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different livers in each group.
2024-04-09 | GSE221443 | GEO
Project description:Dyslipidemia and inflammation play key roles in the pathogenesis of both nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. NAFLD, particularly its severe form nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular disease (CVD) risk. HDL (high density lipoprotein- also a CVD risk) are decreased in NAFLD but whether HDL function is abnormal in NAFLD is unknown. Furthermore, it is unknown whether dyslipidemia contributes to reduced HDL function in NAFLD and whether hepatic inflammation further impairs HDL function in patients with NASH. Therefore, the aim of this study was to investigate HDL function and to examine the effect of dyslipidemia and inflammation on HDL metabolism in patients with biopsy-proven simple steatosis (SS) and NASH. RESULTS: Compared to controls, SS and NASH subjects had significantly higher levels of plasma triglyceride, insulin, and were more insulin resistant (HOMA, P<0.05) with no differences in total cholesterol, HDL cholesterol, ApoB100 and ApoAI levels. NAFLD patients had increased production and degradation rates of both HDLc and ApoAI that resulted in their levels remaining stable. The degradation rates also were increased of other HDL proteins, including ApoAII, ApoAIV, vitamin D-binding protein, and complement 3 (all P<0.05). NAFLD patients had increased activities of LCAT and CETP, indicating altered HDL lipidation. NAFLD induced alterations in HDL metabolism were associated with reduced anti-oxidant but increased pro-inflammatory activity of HDL. However, no differences were observed in either HDL function or the kinetics of HDLc and HDL proteins between SS and NASH subjects.
2019-08-12 | PXD010199 | Pride
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s.
2014-01-03 | GSE53381 | GEO