Dataset Information

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis, where treatment options are limited. As the liver secrets most of the blood plasma proteins its diseases should affect the plasma proteome. Plasma proteome profiling on 48 patients with cirrhosis or NAFLD with normal glucose tolerance or diabetes, revealed 8 significantly changing (ALDOB, APOM, LGALS3BP, PIGR, VTN, IGHD, FCGBP and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts with a 2.7-fold expression change in NAFLD and 4-fold change in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE to NAFLD and cirrhosis. DPP4 is a known drug target in diabetes. ANPEP and TGFBI are of interest because of their potential role in extracellular matrix remodeling in fibrosis.

OTHER RELATED OMICS DATASETS IN: MSV000084332MSV000084333

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Mario Oroshi

LAB HEAD: Matthias Mann

PROVIDER: PXD011839 | Pride | 2019-03-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MaxQuant_Output.zip	Other
	raw_data.zip	Other
	sdrf.tsv	Tabular

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Publications

Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease.

Niu Lili L Geyer Philipp E PE Wewer Albrechtsen Nicolai J NJ Gluud Lise L LL Santos Alberto A Doll Sophia S Treit Peter V PV Holst Jens J JJ Knop Filip K FK Vilsbøll Tina T Junker Anders A Sachs Stephan S Stemmer Kerstin K Müller Timo D TD Tschöp Matthias H MH Hofmann Susanna M SM Mann Matthias M

Molecular systems biology 20190301 3

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin recepto ...[more]

PMID: 30824564

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Project description:Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH. Keywords: Expression profiling by array Male wildtype C57Bl/6 mice were fed LFD or HFD for 21 weeks. Mice were divided into 4 groups based on liver histology.