Perinatal high-fat diet increases hippocampal vulnerability to the adverse effects of subsequent high-fat feeding. (March 2015)

• Record Type: Journal Article
• Authors: Lépinay, Amandine L.; Larrieu, Thomas; Joffre, Corinne; Acar, Niyazi; Gárate, Iciar; Castanon, Nathalie; Ferreira, Guillaume; Langelier, Bénédicte; Guesnet, Philippe; Brétillon, Lionel; Parnet, Patricia; Layé, Sophie; Darnaudéry, Muriel
• Is Part Of: Psychoneuroendocrinology. Volume 53(2015:Mar.)
• Page Start: 82
• Page End: 93
• Publication Date: 2015-03
• Subjects: AUC area under the curve -- C–C control diet throughout life -- C–HF perinatal control diet and high-fat diet at weaning -- DCX doublecortin -- DMA dimethylacetal -- DNMT DNA methyltransferase -- FAs fatty acids -- GD gestational day -- GFAP glial fibrillary acid protein -- HF–C perinatal high-fat diet and control diet at weaning -- HFD high-fat diet -- HF–HF high-fat diet throughout life -- PND postnatal day -- PP post partum -- PUFAs polyunsaturated fatty acids -- TLDA TaqMan low-density array; Memory -- Hippocampus -- Omega-3 fatty acid -- Omega-6 fatty acid -- Water maze -- TaqMan low-density array; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2014.12.008
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: We study the impact of high-fat diet on hippocampal function. Perinatal high-fat, independently of maternal obesity, affects metabolism. Perinatal high-fat affects the hippocampus but not spatial memory. High-fat from conception to adulthood alters hippocampus and memory. High-fat exposure excluding the perinatal period has no impact on spatial memory. Summary: 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.