Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming.
OBJECTIVE
Maternal obesity is associated with increased risk of metabolic dysfunction in the offspring. It is not clear whether it is the metabolic changes or chronic low-grade inflammation in the obese state that causes this metabolic programming. We therefore investigated whether low-grade inflammation was present in obese dams compared with controls dams at gestation day 18 (GD18).


METHODS
Female mice were fed either a standard chow diet or a highly palatable obesogenic diet for 6 weeks before conception. Mice were either kileed before mating (n=12 in each group) or on GD18 (n=8 in each group). Blood and tissues were collected for analysis.


RESULTS
The obesogenic diet increased body weight and decreased insulin sensitivity before conception, while there was no difference between the groups at GD18. Local inflammation was assayed by macrophage count in adipose tissue (AT) and liver. Macrophage count in the AT was increased significantly by the obesogenic diet, and the hepatic count also showed a tendency to increased macrophage infiltration before gestation. This was further supported by a decreased population of monocytes in the blood of the obese animals, which suggested that monocytes are being recruited from the blood to the liver and AT in the obese animals. Gestation reversed macrophage infiltration, such that obese dams showed a lower AT macrophage count at the end of gestation compared with pre-pregnancy obese mice, and there were no longer a tendency toward increased hepatic macrophage count. Placental macrophage count was also similar in the two groups.


CONCLUSIONS
At GD18, obese dams were found to have similar macrophage infiltration in placenta, AT and liver as lean dams, despite an incipient infiltration before gestation. Thus, the obesity-induced inflammation was reversed during gestation.
1] Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark [2] Center for Fetal Programming, Copenhagen, Denmark.
C
C
Ingvorsen
Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
A H
AH
Thysen
University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
D
D
Fernandez-Twinn
Department Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
P
P
Nordby
Department Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
K F
KF
Nielsen
University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
S E
SE
Ozanne
Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark.
S
S
Brix
1] Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark [2] Center for Fetal Programming, Copenhagen, Denmark.
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0000000192154880
LI
Hellgren
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D008099:Liver / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000473:pathology*; D015430:Weight Gain / Q000276:immunology