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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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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DOI: https://doi.org/10.1038/ijo.2012.190
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