Bedeutung des Adipokins CTRP3 für das Fettgewebe und die Entwicklung der Atherosklerose
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Philipps-Universität Marburg
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Abstract
Atherosclerotic cardiovascular disease is the leading cause of death in the Western
world. The metabolic syndrome is highly associated with an increased risk of the
development of atherosclerosis. Excessive food intake leads to hypertrophy and
inflammation of adipose tissue, a condition characterised by an imbalance of adipokine
secretion that causes systemic metabolic alterations.
CTRP3 is an anti-inflammatory adipokine. Decreased levels of CTRP3 are associated
with metabolic and cardiovascular diseases and are a predictor of total mortality.
However, there has been little experimental research on the relation between CTRP3
and the development of these diseases in vivo.
In order to analyse the function of CTRP3, adipocyte-specific CTRP3-KO mice were
fed with a high-fat diet for 6 and 12 weeks respectively and compared to a control
group without CTRP3-KO.
After 6 weeks of high-fat diet feeding, deficiency of CTRP3 led to an increased weight
gain and body fat mass. This was accompanied by an increased adipocyte size and
macrophage infiltration into adipose tissue. After 12 weeks of feeding, none of these
differences could be observed.
Furthermore, elevated plasma VLDL and total cholesterol levels were detected. After
12 weeks of feeding, none of these alterations could be identified. An impact of CTRP3
deficiency on fasting glucose, glucose tolerance and insulin sensitivity could not be
overserved.
With regards to atherosclerosis, CTRP3-KO mice demonstrated an increase in aortic
plaque burden after both 6 and 12 weeks. Moreover, CTRP3-KO mice showed an
increased lipid content in the aortic root and an increased macrophage plaque
infiltration. There was no difference in the necrotic core area.
In addition to the analysis of CTRP3-KO mice, the expression of CTRP3-mRNA in
CTRP3-WT mice was analysed to gain an overview of CTRP3 distribution. Overall, the
aorta showed the highest expression of CTRP3 out of all organs tested.
Further research should focus on markers of systemic inflammation in CTRP3-KO mice
and on the application of recombinant CTRP3 to assess reversibility of the observed
alterations.
The alignment between CTRP3-KO mice and CTRP3-WT mice in terms of the
metabolic phenotype after 12 weeks of feeding may be attributed to decreased food intake of CTRP3-KO mice or an acquired decrease or loss of function of CTRP3 in
CTRP3-WT mice and should be subject to further analysis.
Although CTRP3 is predominantly considered as an adipokine, CTRP3 is also
expressed in other organs than adipose tissue. Concerning atherosclerosis, particularly
the role of CTRP3 expression in the aorta needs to be clarified.
In conclusion, this work reveals that CTRP3 deficiency contributes to hypertrophy and
inflammation of adipose tissue, elevated plasma cholesterol concentrations as well as
the development of atherosclerosis.
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Dates
Created: 2021Issued: 2022-01-20Updated: 2022-01-20
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
DFG-subjects
Adipokin Atherosklerose Fettgewebe
DDC-Numbers
610
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Koch, Sören: Bedeutung des Adipokins CTRP3 für das Fettgewebe und die Entwicklung der Atherosklerose. : Philipps-Universität Marburg 2022-01-20. DOI: https://doi.org/10.17192/z2022.0025.