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Experiment

Experiment for Order #1810
Summary Data Summary
Investigator Minze, Laurie
Description Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity
that can progress to nonalcoholic steatohepatitis (NASH), a serious liver
pathology that can advance to cirrhosis. The mechanisms responsible for NAFLD
progression to NASH remain unclear. Lack of a suitable animal model that
faithfully recapitulates the pathophysiology of human NASH is a major obstacle
in delineating mechanisms responsible for progression of NAFLD to NASH and,
thus, development of better treatment strategies. We identified and
characterized a novel mouse model, middle-aged male LDLR-/- mice fed high-fat
diet (HFD), which developed NASH associated with 4 of 5 metabolic syndrome (MS)
components. In MS mice, as observed in humans, liver steatosis and oxidative
stress promoted NASH development. Aging exacerbated the HFD-induced NASH such
that liver steatosis, inflammation, fibrosis, oxidative stress and liver injury
markers were greatly enhanced in middle-aged versus young LDLR-/- mice. While
expression of genes mediating fatty acid oxidation and antioxidant responses
were upregulated in young LDLR-/- mice fed HFD, they were drastically reduced in
MS mice. However, similar to recent human trials, NASH was partially attenuated
by an insulin-sensitizing peroxisome proliferator-activated receptor-gamma
(PPAR?) ligand, rosiglitazone. In addition to expected improvements in MS, newly
identified mechanisms of PPAR? ligand effects included stimulation of
antioxidant gene expression and mitochondrial ß-oxidation, and suppression of
inflammation and fibrosis. LDLR-deficiency promoted NASH, since middle-aged
C57BL/6 mice fed HFD did not develop severe inflammation and fibrosis, despite
increased steatosis.

Applicable research area(s): Obesity, Cardiovascular, Metabolism
Status Completed
Public Release 5/25/2012
Animal Age Measured In: month(s) post-natal (m)
Flags has-data-flagSame StrainAnimal CountExperiment Description
Data Analysis
TypeCount
Animals31
Experimental Conditions1
Catalog Items5
Curation Info (# flags)3
Phenotype Assays6
Phenotype Measurements186
Histology Images0
Publications0
Phenotypes4


Animals
Strain NameCommon NameFemalesMalesUnknown
C57BL/6J
0
7
0
C57BL/6J-Ldlr-/-
0
24
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


No documents found.


Mammalian Phenotype (MP) Terms
MPTermIDMPTermNameDefinitionOther Results
MP:0001552increased circulating triglyceride level
greater concentration of naturally occurring esters of three fatty acids and glycerol in the blood; triglycerides are widespread in adipose tissue| commonly circulate in the blood in the form of lipoproteins| and are involved in the process of bidirectional transference of adipose fat and blood glucose with the liver [MGI:csmith]
MMPC Search Results
MP:0002941increased circulating alanine transaminase level
increased concentration in the blood of the enzyme which transfers amino groups from l-alanine to 2 ketoglutarate| or the reverse (from l-glutamate to pyruvate); serum concentration is increased in viral hepatitis and myocardial infarction [ISBN:0-683-40008-8| MGI:pvb]
MMPC Search Results
MP:0005178increased circulating cholesterol level
greater than the normal amount in the blood of the principal sterol of vertebrates and the precursor of many steroids| including bile acids and steroid hormones; it is a component of the plasma membrane lipid bilayer and of plasma lipoproteins and can be found in all animal tissues [MGI:csmith]
MMPC Search Results
MP:0005343increased circulating aspartate transaminase level
greater than normal concentration in the blood of this enzyme| which catalyzes the reversible transfer of an amine group from l-glutamic acid to oxaloacetic acid| forming alpha-ketoglutaric acid and l-aspartic acid; aids in diagnosis of viral hepatitis and myocardial infarction [ISBN:0-683-40008-8| MGI:pvb]
MMPC Search Results

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