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Animal Models

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

International Journal of Obesity volume 37, pages 1169–1176 (2013)Cite this article

Subjects

Abstract

Objective:

To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life.

Methods:

During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks.

Results:

WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor γ and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age.

Conclusion:

Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

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Acknowledgements

The research leading to these results has received funding from the European Union’s Seventh Framework Program FP7 2007-2013 under grant agreement no 244995 (BIOCLAIMS Project). It has also been supported by a grant from the Spanish Government (AGL2009-11277/ALI to A.P.). The UIB laboratory is a member of The European Nutrigenomics Organization (NuGO). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the ISCIII (Spanish Government). HM is the recipient of a grant from the Balearic Islands Government. The authors deeply thank Dr Teresa Priego for her advice in the statistical analysis.

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Author notes

  1. N Granados and J Amengual: These two authors contributed equally to this work

Authors and Affiliations

  1. Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, University of the Balearic Islands and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain

    N Granados, J Amengual, J Ribot, H Musinovic, E Ceresi, A Palou & M L Bonet

  2. Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    J Amengual & J von Lintig

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  1. N Granados
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  2. J Amengual
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Correspondence to A Palou.

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Granados, N., Amengual, J., Ribot, J. et al. Vitamin A supplementation in early life affects later response to an obesogenic diet in rats. Int J Obes 37, 1169–1176 (2013). https://doi.org/10.1038/ijo.2012.190

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