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Animal Models

Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner

Abstract

Background/Objectives:

The current world-wide obesity epidemic partially results from a vicious circle whereby maternal obesity during pregnancy predisposes the offspring for accelerated weight gain and development of metabolic syndrome. Here we investigate whether low-grade inflammation, characteristic of the obese state, provides a causal role for this disastrous fetal programming in mice.

Methods:

We exposed pregnant and lactating C57BL/6JBom female mice to either high-fat diet (HFD), or continuous infusion of lipopolysaccharide (LPS), a potent trigger of innate immunity, and studied offspring phenotypes.

Results:

Both maternal LPS or HFD treatments rendered the offspring hyperphagic and inept of coping with a HFD challenge during adulthood, increasing their adiposity and weight gain. The metabolic effects were more pronounced in female offspring, while exposed male offspring mounted a larger inflammatory response to HFD at adulthood.

Conclusions:

This supports our hypothesis and highlights the programming potential of inflammation in obese pregnancies.

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Acknowledgements

We thank Niels Jessen, Gitte Marie Rasmussen and Christian Buhl for help during experimental setup and design and Heidi M Jensen and Rasmus Buchanan for help with animal care. The study was funded by The Danish Council for Independent Research, Medical Sciences, and by the Toyota Foundation. AD was supported by the Graduate School of Science and Technology, Aarhus University.

Author contributions

AD, TW and SL conceived and designed the work; AD, KSH, MK, MH, GWint, BE, ALN and MKN acquired the data and participated in data analysis; AD, KSH, MK, BE, GWeg, ALN, AL, SBP, TW and SL interpreted the results. AD wrote the manuscript draft and all authors participated in manuscript revision and have read and approved the final draft.

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Correspondence to A Dudele.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Dudele, A., Hougaard, K., Kjølby, M. et al. Chronic maternal inflammation or high-fat-feeding programs offspring obesity in a sex-dependent manner. Int J Obes 41, 1420–1426 (2017). https://doi.org/10.1038/ijo.2017.136

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