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

Published online by Cambridge University Press:  02 February 2016

E. J. Tarling
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
K. J. P. Ryan
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
R. Austin
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
S. J. Kugler
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
A. M. Salter
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
S. C. Langley-Evans*
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, UK
*
*Address for correspondence: Professor S. C. Langley-Evans, School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK. (Email [email protected])

Abstract

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, programed 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 28 days 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 with 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 two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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