Liver X receptor (LXR), farnesoid X receptor (FXR) and peroxisome
proliferator-activated receptor (PPAR) are adopted orphan nuclear receptors that
function as lipid sensors. These receptors respond to cellular lipid levels and
regulate the expression of target gene. Previously, it was demonstrated that low
doses of chlordecone (CD) pretreatment disturbed exogenous cholesterol
distribution and cellular lipid transport, storage and metabolism pathway.
The aim of this study was to determine whether low doses of CD affect
nuclear receptor (LXR��/FXR or PPAR��)-mediated lipid homeostasis. Thus,
hepatic microsomal protein contents of cytochrome P450 7a (cyp7a, regulated by
LXR��/FXR), and P450 4a1 (cyp4a1, regulated by PPAR��) were determined in
male C57BL/6N mice, fed AIN76 or AIN93M diet, received CD (2.5, 5.0 or 15 mg
CD/kg body weight). Western blot analysis was used for protein measurements
using appropriate antibodies. Cyp7a and cyp4a1 protein levels were confirmed by
enzyme activities, cholesterol 7��-hydroxylase and lauric acid hydroxylase
activities, respectively. Plasma total cholesterol and triglycerides, body and liver
weights were also measured in these dose-response experiments.
Plasma total cholesterol and triglycerides levels from animals fed AIN 93M
diet were significantly lower than those from animals fed AN 76 diet. However,
neither total plasma cholesterol nor triglycerides levels were changed in CD-treated
mice fed AN 76 or AN 93M diet. Cyp7a protein level or its enzyme activity was
not altered by CD treatment. Likewise, cyp4a1 protein level or its activity was not
affected by CD treatment.
In summary, the results of the present study do not support the hypothesis
that CD treatment alters nuclear receptor (LXR��/FXR or PPAR��)-mediated lipid
homeostasis. / Graduation date: 2002
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/32450 |
| Date | 03 April 2002 |
| Creators | Lee, JungA |
| Contributors | Curtis, Lawrence R. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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