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Animal Models

Fetal growth restriction promotes physical inactivity and obesity in female mice

International Journal of Obesity volume 39, pages 98–104 (2015)Cite this article

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Abstract

Background:

Environmental exposures during critical periods of prenatal and early postnatal life affect the development of mammalian body weight regulatory mechanisms, influencing lifelong risk of obesity. The specific biological processes that mediate the persistence of such effects, however, remain poorly understood.

Objective:

The objectives of this study were to determine the developmental timing and physiological basis of the obesity-promoting effect previously reported in offspring of obese agouti viable yellow (Avy/a) mothers.

Design:

Newborn offspring of obese Avy/a and lean (a/a) mothers were cross-fostered shortly after birth to study separately the effects of in utero or suckling period exposure to Avy/a dams. Body composition, food intake, physical activity and energy expenditure were measured in offspring shortly after weaning and in adulthood.

Results:

Offspring of obese Avy/a dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically in females. Our main analyses focused on wild-type (a/a) offspring, because a subset of adult Avy/a offspring contracted a kidney disease resembling diabetic nephropathy. Detailed physiological characterization demonstrated that, both shortly after weaning and in adulthood, female wild-type mice born to Avy/a mothers are not hyperphagic but have reduced physical activity and energy expenditure. No such coordinated changes were detected in male offspring. Mediational regression analysis of our longitudinal data supported a causal pathway in which fetal growth restriction persistently reduces physical activity, leading to adult obesity.

Conclusions:

Our data are consistent with several recent human epidemiological studies showing female-specific effects of perinatal nutritional restriction on later obesity, and provide the novel mechanistic insight that this may occur via permanent and sex-specific changes in one’s inherent propensity for physical activity.

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Acknowledgements

We thank Adam Gillum (USDA/ARS CNRC) for assistance with the figures and Firoz Vohra (USDA/ARS CNRC) for assistance with the CLAMS studies. MSB conducted research and wrote the paper; GL and JJK conducted research; RAW designed research, analyzed data, wrote the paper and had primary responsibility for final content. This work was supported by grants from NIH/NIDDK (1R01DK081557) and USDA (CRIS 6250–51000–055) to RAW. The body composition and CLAMS studies were performed in the Mouse Metabolic Research Unit at the USDA/ARS Children’s Nutrition Research Center, which is supported by funds from the USDA/ARS.

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Author notes

  1. J J Kohorst

    Present address: 3Current address: Mayo Medical School, The Mayo Clinic, Rochester, MN, USA.,

Authors and Affiliations

  1. Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children’s Nutrition Research Center, Houston, TX, USA

    M S Baker, G Li, J J Kohorst & R A Waterland

  2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    R A Waterland

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  1. M S Baker
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Correspondence to R A Waterland.

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Baker, M., Li, G., Kohorst, J. et al. Fetal growth restriction promotes physical inactivity and obesity in female mice. Int J Obes 39, 98–104 (2015). https://doi.org/10.1038/ijo.2013.146

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