Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis. Human liver samples of steatosis and non-alcoholic steatohepatitis were selected for RNA extraction and hybridization on Affymetrix microarrays. This dataset is part of the TransQST collection.
Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis.
Project description:Mardinoglu2014 - Genome-scale metabolic model
(HMR version 2.0) - human hepatocytes (iHepatocytes2322)
This model is described in the article:
Genome-scale metabolic
modelling of hepatocytes reveals serine deficiency in patients
with non-alcoholic fatty liver disease.
Mardinoglu A, Agren R, Kampf C,
Asplund A, Uhlen M, Nielsen J.
Nat Commun 2014; 5: 3083
Abstract:
Several liver disorders result from perturbations in the
metabolism of hepatocytes, and their underlying mechanisms can
be outlined through the use of genome-scale metabolic models
(GEMs). Here we reconstruct a consensus GEM for hepatocytes,
which we call iHepatocytes2322, that extends previous models by
including an extensive description of lipid metabolism. We
build iHepatocytes2322 using Human Metabolic Reaction 2.0
database and proteomics data in Human Protein Atlas, which
experimentally validates the incorporated reactions. The
reconstruction process enables improved annotation of the
proteomics data using the network centric view of
iHepatocytes2322. We then use iHepatocytes2322 to analyse
transcriptomics data obtained from patients with non-alcoholic
fatty liver disease. We show that blood concentrations of
chondroitin and heparan sulphates are suitable for diagnosing
non-alcoholic steatohepatitis and for the staging of
non-alcoholic fatty liver disease. Furthermore, we observe
serine deficiency in patients with NASH and identify PSPH,
SHMT1 and BCAT1 as potential therapeutic targets for the
treatment of non-alcoholic steatohepatitis.
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MODEL1402200003.
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Project description:Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.
Project description:The liver plays a central role in whole body metabolic regulation. Studies of liver metabolism are mostly done in vivo in animal models due to the lack of reliable in vitro systems that can recapitulate liver metabolic functions and their regulation. Hepatocyte organoids (HOs) generated in vitro recently are powerful tools for liver regeneration. Here we developed a novel culture condition that enabled successful generation of mature hepatocyte organoids (MHOs) with metabolic functions characteristic of adult livers. We showed that the MHOs can be used to study gene expression that exhibit zonal patterns in vivo, hepatic proliferation during tumorigenesis and metabolic alterations in disorders of both alcoholic and non-alcoholic fatty liver diseases.
Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans.
Project description:The extent to which PTP (Protein tyrosine phosphatase) expression may be evident and contribute to the progression to non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) in obesity and the development of hepatocellular carcinoma (HCC) remains unknown. We conducted a comprehensive analysis of the total proteome and PTP expression patterns, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of human liver samples. The cohort included liver biopsies obtained from individuals presenting varying degrees of liver disease, encompassing steatosis, Non-alcoholic steatohepatitis (NASH), HCC, and control samples from individuals without evidence of liver damage.
2024-09-24 | PXD046940 | Pride
Project description:Research on non-alcoholic fatty liver disease