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Animal Models

Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse male offspring in an obesogenic environment

International Journal of Obesity volume 40, pages 1875–1883 (2016)Cite this article

Subjects

Abstract

Background/Objectives:

Vitamin D is an anti-inflammatory nutrient and a determinant of bone health. Some prospective studies suggest that maternal vitamin D status is positively associated with offspring bone mass. We found that serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule related to adiposity, insulin resistance and bone resorption, is lower in healthy mouse offspring exposed to high dietary vitamin D during pregnancy and lactation. LPS reaches the circulation via the gut. This study investigated whether maternal vitamin D programs metabolic, gut and bone health of male offspring in an obesogenic environment.

Methods:

C57BL/6J dams received an AIN-93G diet with high (H) or low (L) vitamin D during pregnancy and lactation. At weaning, offspring remained on their dam’s vitamin D level (LL or HH) or were switched (LH or HL) and fed a high fat (44.2%) and sucrose (19.8%) diet. Glucose response, adiposity, systemic inflammation (LPS, cytokines), intestinal permeability and mass, strength and microarchitecture of trabecular and cortical bone were assessed in 7-month-old male offsprings.

Results:

Higher maternal dietary vitamin D resulted in lower intestinal permeability (fecal albumin, P=0.010) and benefited trabecular but not cortical bone structure at the distal femur (higher trabecular number, P=0.022; less trabecular separation, P=0.015) and lumbar vertebra 2 (bone volume/total volume%, P=0.049). Higher maternal and offspring vitamin D resulted in lower fasting glucose (HH versus LL, P=0.039) and serum LPS concentrations (dam diet, P=0.011; pup diet, P=0.002). Higher offspring vitamin D resulted in lower epididymal fat pad relative weight (P=0.006). The serum concentrations of IL-6 and TNF-α did not differ among groups.

Conclusions:

Maternal dietary vitamin D beneficially programs intestinal permeability and systemic LPS concentration, which is accompanied by stronger trabecular bone in an obesogenic environment. Thus, the gut may mediate vitamin D effects. Moreover, optimizing vitamin D in early life may be critical for later health.

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Acknowledgements

This project was funded by a matching grant from the Centrum Foundation of Pfizer Consumer Healthcare Research Innovation Fund and the Department of Nutritional Sciences at the University of Toronto to EMC and WEW, and from a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant to EMC (Grant # RGPIN 356124-2013). The μCT system was purchased with funding from the Canada Foundation for Innovation to WEW (Grant #222084). Christopher R Villa was partially funded by the Banting and Best Diabetes Centre-Novo Nordisk Studentship and Tamarack Graduate Award in Diabetes Research and by an Ontario Graduate Scholarship. Wendy Ward holds a Canada Research Chair in Bone and Muscle Development. Elena Comelli holds the Lawson Family Chair in Microbiome Nutrition Research at the University of Toronto. We wish to thank Hayley Craig-Barnes of the Analytical Facility for Bioactive Molecules of The Centre for the Study of Complex Childhood Diseases, The Hospital for Sick Children, Toronto, Canada for measurements of serum 25(OH)D3 concentrations.

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Authors and Affiliations

  1. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    C R Villa, J Chen, B Wen, A Taibi, W E Ward & E M Comelli

  2. Department of Kinesiology, Faculty of Applied Health Sciences, Brock University, St. Catharines, ON, Canada

    S M Sacco & W E Ward

  3. Centre for Child Nutrition and Health, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    E M Comelli

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Correspondence to E M Comelli.

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Villa, C., Chen, J., Wen, B. et al. Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse male offspring in an obesogenic environment. Int J Obes 40, 1875–1883 (2016). https://doi.org/10.1038/ijo.2016.177

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