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Experiment

Circulating corticosterone levels in Ncor1D mice
Summary Data Summary
Investigator Privalsky, Martin
Description Corticosterone assay for determining levels in mouse serum samples

We previously showed that two thyroid hormone receptor (TR) isoforms ? TRa1 and
TRß1 ? differentially regulate thyroid hormone (triiodothyroxine, T3)-stimulated
adipogenesis in vivo. This study aims to understand the role of the nuclear
receptor corepressor, NCoR1, in TR isoform-dependent adipogenesis. We found that
T3-stimulated adipogenesis of 3T3-L1 cells was accompanied by progressive loss
of NCoR1 protein levels. In 3T3-L1 cells stably expressing a mutated TRa1, PV
(L1-a1PV cells), the T3-stimulated adipogenesis was more strongly inhibited than
that in 3T3-L1 cells stably expressing an identical mutation in TRß1 (L1-ß1 PV
cells). The stronger inhibition of adipogenesis in L1-a1 PV cells was associated
with a higher NCoR1 protein level. These results indicate that the degree of
loss of NCoR1 correlates with the extent of adipogenesis. siRNA knockdown of
NCoR1 promoted adipogenesis of control 3T3-L1 cells and reversed the inhibited
adipogenesis of L1-a1PV and L1-ß1PV cells, indicating that NCoR1 plays an
essential role in TR isoform-dependent adipogenesis. An ubiquitin ligase,
mSiah2, that targets NCoR1 for proteasome degradation was upregulated on day 1
before the onset of progressive loss of NCoR1. NCoR1 was found to associate with
mSiah2 and with TR, TRa1 PV, or TRß1 PV, but a stronger interaction of NCoR1
with TRa1 PV than with TRß1 PV was detected. Furthermore, TRa1 PV?NCoR1 complex
was more avidly recruited than TRß1 PV?NCoR1 to the promoter of the C/ebpa gene,
leading to more inhibition in its expression. These results indicate that
differential interaction of NCoR1 with TR isoforms accounted for the TR
isoform-dependent regulation of adipogenesis and that aberrant interaction of
NCoR1 with TR could underlie the pathogenesis of lipid disorders in
hypothyroidism.
Status Completed
Public Release 2/14/2015
Animal Age Measured In: week(s) post-natal (w)
Flags has-data-flagAnimal CountExperiment Description
Data Analysis
TypeCount
Animals17
Experimental Conditions6
Catalog Items1
Curation Info (# flags)2
Phenotype Assays1
Phenotype Measurements34
Histology Images0
Publications0
Documents1


Animals

Strain NameCommon NameFemalesMalesUnknown
C57BL/6
0
6
0
NCoR omega
0
6
0
NCoR delta
0
5
0


Experimental Factors
 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: Fast Duration (hr)

 fast duration
Length of time the animal was fasted

Experimental Factor: Feeding Group

 Fasted
Animals are deprived of food but not water.
 Fed
Animals are allowed to have food.

Experimental Factor: Mouse Diet

 Research Diets - D12492
Rodent Diet with 34% Fat, 60% kcal from Fat

Experimental Factor: Time Sample Taken (min)

 Time Sample Taken
Time in minutes since a sample was taken

Experimental Factor: Tissue Source

 serum
serum


Phenotype Assays Add / Edit


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