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Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming

International Journal of Obesity volume 38, pages 1282–1289 (2014)Cite this article

Subjects

Abstract

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.

Conclusion:

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.

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Acknowledgements

This study was supported by Otto Moensted foundation 11-70-0597, Aase and Ejnar Danielsen foundation10-000473, Reinholdt W. Jorck and wife’s foundation 11-Ji-0230 and Master of Engineering Frants Allings foundation, the Danish Strategic Research Council through Grant no 09-067124 to ‘Centre for Fetal Programming’ (LIH), as well as the EU FP7 Early Nutrition project Grant no: 289346 to SEO who is also a member of the MRC Metabolic Diseases Unit. Jannie F Agersten and Anne-Marie Nepper are acknowledged for skillful technical assistance in the lipid analysis and Lisbeth Buus Rosholm for cytokine analysis.

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Authors and Affiliations

  1. Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark

    C Ingvorsen, A H Thysen, S Brix & L I Hellgren

  2. Center for Fetal Programming, Copenhagen, Denmark

    C Ingvorsen & L I Hellgren

  3. University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK

    D Fernandez-Twinn & S E Ozanne

  4. Department Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark

    P Nordby & K F Nielsen

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  1. C Ingvorsen
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Correspondence to L I Hellgren.

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Ingvorsen, C., Thysen, A., Fernandez-Twinn, D. et al. Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming. Int J Obes 38, 1282–1289 (2014). https://doi.org/10.1038/ijo.2014.69

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