Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Tarling, Elizabeth J. and Ryan, K.J.P. and Austin, Ruth Marie and Kugler, Susanne J. and Salter, Andrew M. and Langley-Evans, Simon C. Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse. Journal of the Developmental Origins of Health and Disease . ISSN 2040-1752 (In Press)

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Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.

Item Type: Article
Schools/Departments: University of Nottingham UK Campus > Faculty of Science > School of Biosciences
Depositing User: Langley-Evans, Simon
Date Deposited: 06 Jan 2016 09:28
Last Modified: 15 Sep 2016 12:43

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