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Experiment

Experiment for Order #1815
Summary Data Summary
Investigator Minze, Laurie
Description We recently identified and phenotyped a ‘MS mouse’, middle-aged (12-month-old)
male LDLR-/- mice fed 3 months of HFD, that developed 4 of 5 criteria of human
MS. These mice not only developed worse MS and diabetes than HFD-fed young
(3-month-old) LDLR-/- mice, but also developed worse atherosclerosis, which
correlated with a profound failure of vascular antioxidant defense systems.
Since a ‘two-hit’ theory has been proposed for the progression of NAFLD to NASH:
hepatic steatosis associated with MS being the first hit, followed by a second
insult from increased oxidative stress, we hypothesized that the MS mouse
represents a useful model of the progression of NAFLD to NASH. We report herein
that MS mice developed NASH with all the histologic characteristics of human
disease, including age-dependency and attenuation in response to treatment with
the PPARgamma ligand rosiglitazone (RSG). Newly identified actions of RSG
included reduction of liver oxidative stress by up-regulation of expression of
nuclear factor- (erythroid-derived 2)-like 2 (Nrf2), a “master” regulator of the
anti-oxidant response, stimulation of liver mitochondrial fatty acid
ß-oxidation, and inhibition of inflammation and fibrosis, all of which appear
independent of its systemic insulin-sensitizing effects. These observations have
implications for development of new strategies to prevent and treat this
increasingly common cause of end stage liver disease.

Applicable research area(s): Diabetes, Obesity, Metabolism, Cardiovascular
Status Completed
Public Release 5/25/2012
Data Collected? Data will not be collected for this catalog item
Animal Age Measured In: month(s) post-natal (m)
Flags has-data-flagSame StrainAnimal CountExperiment Description
Data Analysis
TypeCount
Animals27
Experimental Conditions1
Catalog Items1
Curation Info (# flags)3
Phenotype Assays2
Phenotype Measurements54
Histology Images0
Publications0
Phenotypes2


Animals
Strain NameCommon NameFemalesMalesUnknown
C57BL/6J
0
8
0
C57BL/6J-Ldlr-/-
0
19
0

Animals/Strains
Experimental Factors
 Categorical Values
Name / AbbreviationDescription

Experimental Factor: Experimental Group

 Control
This animal belongs to the control group for the experiment.
 Experiment
This animal belongs to experimental group that is homozygous for gene manipulations.
Experimental Factor (Units)
Experimental Group
Experimental Factor Values


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