Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Multi-Omics Data Integration Reveals Sex-Dependent Hippocampal Programming by Maternal High-Fat Diet during Lactation in Adult Mouse Offspring

Thibaut Gauvrit
,
Hamza Benderradji
,
Alexandre Pelletier
,
Soulaimane Aboulouard
ORCID logo ,
Emilie Faivre
,
Kevin Carvalho
,
Aude Deleau
,
Emmanuelle Vallez
,
Agathe Launay
,
Anna Bogdanova
,
Mélanie Besegher
,
Stéphanie Le Gras
,
Anne Tailleux
,
Michel Salzet
,
Luc Buée
ORCID logo ,
Fabien Delahaye
,
David Blum
,
Didier Vieau
* ORCID logo
Version 1 : Received: 6 October 2023 / Approved: 9 October 2023 / Online: 9 October 2023 (13:18:25 CEST)

A peer-reviewed article of this Preprint also exists.

Gauvrit, T.; Benderradji, H.; Pelletier, A.; Aboulouard, S.; Faivre, E.; Carvalho, K.; Deleau, A.; Vallez, E.; Launay, A.; Bogdanova, A.; Besegher, M.; Le Gras, S.; Tailleux, A.; Salzet, M.; Buée, L.; Delahaye, F.; Blum, D.; Vieau, D. Multi-Omics Data Integration Reveals Sex-Dependent Hippocampal Programming by Maternal High-Fat Diet during Lactation in Adult Mouse Offspring. Nutrients 2023, 15, 4691. Gauvrit, T.; Benderradji, H.; Pelletier, A.; Aboulouard, S.; Faivre, E.; Carvalho, K.; Deleau, A.; Vallez, E.; Launay, A.; Bogdanova, A.; Besegher, M.; Le Gras, S.; Tailleux, A.; Salzet, M.; Buée, L.; Delahaye, F.; Blum, D.; Vieau, D. Multi-Omics Data Integration Reveals Sex-Dependent Hippocampal Programming by Maternal High-Fat Diet during Lactation in Adult Mouse Offspring. Nutrients 2023, 15, 4691.

Abstract

Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cognitive parameters in young adult offspring mice. To identify early-programming mechanisms in hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, a mild glucose intolerance only in 3-month-old male mice with no change in plasma metabolic parameters in adult male and female offspring. Behavioral alterations revealed by Barnes maze test were observed both in 6-month-old male and female mice. Multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies that were confirmed by regulon analysis, showing that, although genes whose expression was modified by maternal HF were different between sexes, the main pathways affected were similar with mitochondria and synapses as main hippocampal targets of maternal HF. The effects of maternal HF reported here may help to better characterize sex-dependent molecular pathways involved in cognitive disorders and neurodegenerative diseases.

Keywords

Maternal high-fat diet; multiomics; sexual dimorphism; hippocampus

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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