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| Status |
Public on Sep 09, 2010 |
| Title |
Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57Bl/6 mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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
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| Overall design |
Male wildtype C57Bl/6 mice were fed LFD or HFD for 21 weeks. Mice were divided into 4 groups based on liver histology.
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| Web link |
http://humannutrition2.wur.nl/duval2010/
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| Contributor(s) |
Duval C, Thissen U, Keshtkar S, Accard B, Stienstra R, Boekschoten M, Roskams T, Kersten S, Müller M |
| Citation(s) |
20858684 |
| Submission date |
Sep 08, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA130277 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24031_RAW.tar |
61.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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