genomewide characterization of host-pathogen interactions by ...

triglycerides [mmol/l]
cholesterol [mmol/l]
HDL [mmol/l]
VLDL [mmol/l]
LDL [mmol/l]
Maren Depke
Results
Liver Gene Expression Pattern in a Mouse Psychological Stress Model
reduced concentrations of several essential amino acids, e. g. arginine, threonine, methionine,
and tryptophan, whereas nonessential amino acids showed fewer alterations in repeatedly
stressed mice (Depke et al. 2008: supplemental material 5 at http://endo.endojournals.org). In
addition, gene expression profiling of the liver of repeatedly stressed mice showed an induction
of genes for amino acid transporters and amino acid metabolizing enzymes (Sds, Slc15a4,
Slc25a15, Slc3a1, Got1, and Tat), and provided hints for increased activation of amino acid
degradation pathways (Aass, Ahcy, Asl, Prodh, and Tdo2). The induction of Asl expression along
with a loss of arginine and citrulline in the plasma (Depke et al. 2008: supplemental material 5 at
http://endo.endojournals.org) provided hints for altered urea cycle activity. This substantiates
the observations of systemic usage of the body’s protein stores in repeatedly stressed BALB/c
mice. In contrast, after a single acute stress session, mRNA expression of only a few glucogenic
amino acid transporters and metabolizing enzymes was induced in the liver (Sds, Slc38a2, and
Tat), which did not result in altered amino acid levels in the periphery (data not shown).
A
B
C D E F G
4
3.5 **
***
3
3.0
2
2.5
1
2.0
3.0
***
0.3 ***
2.5
0.2
2.0
0.1
0.4
0.3
0.2
0.1
0
1.5
1.5
0
0
Fig. R.1.5: Disturbances of fat metabolism in repeatedly stressed mice.
A, B. Hepatic steatosis in repeatedly stressed mice (A) compared with nonstressed mice (B) (HE staining magnification, x20); each
picture is representative for nine mice per group.
C–G. Plasma fat composition of repeatedly stressed mice (black box plots) and nonstressed controls (white box plots); triglyceride
levels (C), total cholesterol (D), HDL-cholesterol (E), VLDL-cholesterol (F), and LDL-cholesterol (G) were measured immediately after
the ninth stress session (n = 12 mice per group). ** p < 0.01; *** p < 0.001, Mann-Whitney U test.
Stress-induced alterations of hepatic gene expression of immune response genes after acute
and chronic stress
The analysis of liver homogenates of acutely and chronically stressed mice revealed an altered
mRNA expression of some immune response genes. Here, canonical pathway analysis of
Ingenuity Pathway Analysis (IPA, www.ingenuity.com) was applied to gain a deeper insight in the
mechanism of stress-induced alterations of immune functions after acute or repeated
psychological stress. Looking at the effects of acute stress, ranking of canonical pathways by IPA
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