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

Author:

Gauvrit Thibaut12ORCID,Benderradji Hamza12ORCID,Pelletier Alexandre3ORCID,Aboulouard Soulaimane4ORCID,Faivre Emilie12,Carvalho Kévin12,Deleau Aude12,Vallez Emmanuelle5,Launay Agathe12,Bogdanova Anna12,Besegher Mélanie6,Le Gras Stéphanie7,Tailleux Anne5,Salzet Michel4,Buée Luc12ORCID,Delahaye Fabien8,Blum David12,Vieau Didier12ORCID

Affiliation:

1. UMR-S1172, Lille Neurosciences & Cognition, University of Lille, INSERM, CHU Lille, 59000 Lille, France

2. Alzheimer & Tauopathies, LabEX DISTALZ, 59045 Lille, France

3. The Department of Pharmacology & Biophysics, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA 02118, USA

4. U1192—Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), University of Lille, INSERM, 59000 Lille, France

5. Institut Pasteur de Lille, U1011-EGID, University of Lille, INSERM, CHU Lille, 59000 Lille, France

6. US 41-UMS 2014-PLBS, Animal Facility, University of Lille, CNRS, INSERM, CHU Lille, 59000 Lille, France

7. CNRS U7104, INSERM U1258, GenomEast Platform, IGBMC, University of Strasbourg, 67412 Illkirch, France

8. Sanofi Precision Medicine and Computational Biology, 94081 Vitry-sur-Seine, France

Abstract

Early-life exposure to high-fat diets (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies have 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 the hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, and 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 a Barnes maze test were observed both in 6-month-old male and female mice. The multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies that were confirmed by regulon analysis show 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.

Funder

Programme d’Investissements d’Avenir LabEx (excellence laboratory) DISTALZ

ANR METABOTAU

Publisher

MDPI AG

Subject

Food Science,Nutrition and Dietetics

Reference88 articles.

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