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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Project description:Non-alcoholic fatty liver disease is linked to disrupted serine metabolism. SHMT2 is a liver enzyme that is crucial for liver methylation and overall health. We developed a mouse strain with targeted SHMT2 knockout in hepatocytes and found that the absence of SHMT2 led to increased circulating serine and glycine levels, 1C deficiency, and depleted liver methylation potential. The study reveals the critical role of SHMT2 in maintaining hepatic 1C homeostasis and regulating the progression of non-alcoholic fatty liver disease.
Project description:DNA methylation analysis in non-alcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients with all stages of NAFLD and controls were analysed by array-based DNA methylation and mRNA expression profiling. Bisulphite converted DNA from the 85 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
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:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients with all stages of NAFLD and controls were analysed by array-based DNA methylation and mRNA expression profiling.
