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Physiology and Biochemistry

Dietary vitamin A supplementation prevents early obesogenic diet-induced microbiota, neuronal and cognitive alterations

Subjects

Abstract

Background

Early consumption of obesogenic diets, rich in saturated fat and added sugar, is associated with a plethora of biological dysfunctions, at both peripheral and brain levels. Obesity is also linked to decreased vitamin A bioavailability, an essential molecule for brain plasticity and memory function.

Methods

Here we investigated in mice whether dietary vitamin A supplementation (VAS) could prevent some of the metabolic, microbiota, neuronal and cognitive alterations induced by obesogenic, high-fat and high-sugar diet (HFSD) exposure from weaning to adulthood, i.e. covering periadolescent period.

Results

As expected, VAS was effective in enhancing peripheral vitamin A levels as well as hippocampal retinoic acid levels, the active metabolite of vitamin A, regardless of the diet. VAS attenuated HFSD-induced excessive weight gain, without affecting metabolic changes, and prevented alterations of gut microbiota α-diversity. In HFSD-fed mice, VAS prevented recognition memory deficits but had no effect on aversive memory enhancement. Interestingly, VAS alleviated both HFSD-induced higher neuronal activation and lower glucocorticoid receptor phosphorylation in the hippocampus after training.

Conclusion

Dietary VAS was protective against the deleterious effects of early obesogenic diet consumption on hippocampal function, possibly through modulation of the gut–brain axis.

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Fig. 1: Effects of VAS and HFSD on weight gain and metabolic markers.
Fig. 2: Effects of VAS and HFSD on memory.
Fig. 3: Effects of VAS and HFSD on hippocampus after training.
Fig. 4: Effects of VAS and HFSD on microbiota.

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Acknowledgements

The authors thank all the personnel of the Animal Facility of NutriNeuro for mouse care. We also thank Sofia Cussotto and Claire de La Serre for useful discussions about microbiota analysis, Dr. H. Vaudry for providing the anti-corticosterone antibody, Corinne Buré for the RA measurements at the Bordeaux Functional Genomics Center and Yann Rufin for helping with the Western blot analysis at the Biochemistry and Biophysics Platform of Bordeaux Neurocampus Center.

Funding

This research was supported through the Joint Project Initiative “Healthy Diet for Healthy Life” joint funding action (JPI HDHL JFA) “Nutrition and Cognitive Function (NutriCog)” entitled ‘AMBROSIAC—A Menu for Brain Responses Opposing Stress-Induced Alterations in Cognition’ (ANR-15-HDHL-0001-03 to LC, the Science Foundation Ireland Proposal 15/JP-HDHL/3270 to JC), French National Research Agency (ANR-15-CE17-0013 OBETEEN to GF), INRA (to GF), the Conseil Regional de Nouvelle Aquitaine Bordeaux and INP (to VP). JC, CS and HS are supported by APC Microbiome Ireland, a research center funded by Science Foundation Ireland, through the Irish Government’s National Development Plan (grant no. 12/RC/2273). EFB was the recipient of a PhD fellowship from Bordeaux INP/Conseil Regional de Nouvelle Aquitaine (2016-2019).

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Correspondence to Guillaume Ferreira.

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Biyong, E.F., Alfos, S., Dumetz, F. et al. Dietary vitamin A supplementation prevents early obesogenic diet-induced microbiota, neuronal and cognitive alterations. Int J Obes 45, 588–598 (2021). https://doi.org/10.1038/s41366-020-00723-z

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