title: Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding.
abstract: Epidemiological observations report an increase in fat consumption associated with low intake of n-3 relative to n-6 polyunsaturated fatty acids (PUFAs) in women of childbearing age. However, the impact of these maternal feeding habits on cognitive function in the offspring is unknown. This study aims to investigate the impact of early exposure to a high-fat diet (HFD) with an unbalanced n-6/n-3 PUFAs ratio on hippocampal function in adult rats. Furthermore, we explored the effects of perinatal HFD combined with exposure to HFD after weaning. Dams were fed a control diet (C, 12% of energy from lipids, n-6/n-3 PUFAs ratio: 5) or HFD (HF, 39% of energy from lipids, n-6/n-3 PUFAs ratio: 39) throughout gestation and lactation. At weaning, offspring were placed either on control (C-C, HF-C) or high-fat (HF-HF) diets. In adulthood, hippocampus-dependent memory was assessed using the water-maze task and potential hippocampal alterations were determined by studying PUFA levels, gene expression, neurogenesis and astrocyte morphology. Perinatal HFD induced long-lasting metabolic alterations and some changes in gene expression in the hippocampus, but had no effect on memory. In contrast, spatial memory was impaired in animals exposed to HFD during the perinatal period and maintained on this diet. HF-HF rats also exhibited low n-3 and high n-6 PUFA levels, decreased neurogenesis and downregulated expression of several plasticity-related genes in the hippocampus. To determine the contribution of the perinatal diet to the memory deficits reported in HF-HF animals, an additional experiment was conducted in which rats were only exposed to HFD starting at weaning (C-HF). Interestingly, memory performance in this group was similar to controls. Overall, our results suggest that perinatal exposure to HFD with an unbalanced n-6/n-3 ratio sensitizes the offspring to the adverse effects of subsequent high-fat intake on hippocampal function.
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Amandine L
authors.initials: AL
authors.lastname: Lépinay
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Larrieu
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Joffre
authors.affiliation: CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Iciar
authors.initials: I
authors.lastname: Gárate
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Castanon
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Ferreira
authors.affiliation: INRA, Nutrition et Régulation Lipidique des Fonctions Cérébrales, UR909, 78352 Jouy-en-Josas Cedex, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Langelier
authors.affiliation: PG Consulting, 13 Villa Bellevue, 91440 Bures sur Yvette, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guesnet
authors.affiliation: CNRS, UMR 6265 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; INRA, UMR 1324 Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France; Université de Bourgogne, UMR Centre des Sciences du Goût et de l'Alimentation, 21000 Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Brétillon
authors.affiliation: INRA, UMR 1280, Physiologie des Adaptations Nutritionnelles, 44093 Nantes, France; Université de Nantes, UMR 1280, Physiologie des Adaptations Nutritionnelles, 44093 Nantes, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Parnet
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Layé
authors.affiliation: INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France; Université de Bordeaux, Nutrition et Neurobiologie Intégrée, UMR 1286, 33000 Bordeaux, France. Electronic address: muriel.darnaudery@u-bordeaux.fr.
authors.forename: Muriel
authors.initials: M
authors.lastname: Darnaudéry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059305:Diet, High-Fat; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D007774:Lactation; D018782:Maze Learning / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects*; D014886:Weaning
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6
keywords: Hippocampus; Memory; Omega-3 fatty acid; Omega-6 fatty acid; TaqMan low-density array; Water maze