mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Rosiglitazone attenuates age- and diet-associated nonalcoholic steatohepatitis
in male low-density lipoprotein receptor knockout mice.
Authors Gupte AA, Liu JZ, Ren Y, Minze LJ, Wiles JR, Collins AR, Lyon CJ, Pratico D,
Finegold MJ, Wong ST, Webb P, Baxter JD, Moore DD, Hsueh WA
Submitted By Patrick Tso on 7/6/2011
Status Published
Journal Hepatology (Baltimore, Md.)
Year 2010
Date Published
Volume : Pages 52 : 2001 - 2011
PubMed Reference 20938947
Abstract 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 low-density lipoprotein
receptor (LDLR)(-/-) mice fed a high-fat diet (HFD), which developed NASH
associated with four of five metabolic syndrome (MS) components. In these 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. Although expression of
genes mediating fatty acid oxidation and antioxidant responses were up-regulated
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, because middle-aged
C57BL/6 mice fed HFD did not develop severe inflammation and fibrosis, despite
increased steatosis. Conclusion: MS mice represent an ideal model to investigate
NASH in the context of MS, as commonly occurs in human disease, and NASH
development can be substantially attenuated by PPAR? activation, which enhances
ß-oxidation.




Strains


Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.