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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 ,
K. J. P. Ryan ,
R. Austin ,
S. J. Kugler ,
A. M. Salter  and
S. C. Langley-Evans
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])
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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.

Keywords

animaldevelopmental stagefetussmall animals
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 7 , Issue 3: Themed Issue: Ibero-American DOHaD Society , June 2016 , pp. 290 - 297
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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References

1. Langley-Evans, SC. Nutrition in early life and the programming of adult disease: a review. J Hum Nutr Diet. 2015; 28(Suppl. 1), 1–14.Google Scholar
2. Hanson, MA, Gluckman, PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014; 94, 027–1076.Google Scholar
3. Mone, SM, Gillman, MW, Miller, TL, Herman, EH, Lipshultz, SE. Effects of environmental exposures on the cardiovascular system: prenatal period through adolescence. Pediatrics. 2004; 113(Suppl. 4), 1058–1069.Google Scholar
4. Symonds, ME, Mendez, MA, Meltzer, HM, et al. Early life nutritional programming of obesity: mother-child cohort studies. Ann Nutr Metab. 2013; 62, 137–145.Google Scholar
5. Hales, CN, Barker, DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001; 60, 5–20.Google Scholar
6. Langley-Evans, SC. Developmental programming of health and disease. Proc Nutr Soc. 2006; 65, 97–105.Google Scholar
7. Barker, DJ, Thornburg, KL, Osmond, C, Kajantie, E, Eriksson, JG. Beyond birthweight: the maternal and placental origins of chronic disease. J Dev Orig Health Dis. 2010; 1, 360–364.Google Scholar
8. McMullen, S, Mostyn, A. Animal models for the study of the developmental origins of health and disease. Proc Nutr Soc. 2009; 68, 306–320.Google Scholar
9. Langley, SC, Jackson, AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci. 1994; 86, 217–222.Google Scholar
10. Swali, A, McMullen, S, Hayes, H, et al. Cell cycle regulation and cytoskeletal remodelling are critical processes in the nutritional programming of embryonic development. PLoS One. 2011; 6, e23189.Google Scholar
11. McMullen, S, Langley-Evans, SC. Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R85–R90.Google Scholar
12. Elmes, MJ, Gardner, DS, Langley-Evans, SC. Fetal exposure to a maternal low-protein diet is associated with altered left ventricular pressure response to ischaemia-reperfusion injury. Br J Nutr. 2007; 98, 93–100.Google Scholar
13. Yates, Z, Tarling, EJ, Langley-Evans, SC, Salter, AM. Maternal undernutrition programmes atherosclerosis in the ApoE*3-Leiden mouse. Br J Nutr. 2008; 10, 1–10.Google Scholar
14. Ogden, CL, Carroll, MD, Kit, BK, Flegal, KM. Prevalence of Obesity Among Adults: United States, 2011–2012. NCHS Data Brief, No. 131. 2013. National Center for Health Statistics: Hyattsville, MD.Google Scholar
15. World Health Organization. Obesity and overweight. WHO factsheet 311. Retrieved 28 January 2014 from http://www.who.int/mediacentre/factsheets/fs311/en/.Google Scholar
16. Oken, E, Kleinman, KP, Belfort, MB, Hammitt, JK, Gillman, MW. Associations of gestational weight gain with short- and longer-term maternal and child health outcomes. Am J Epidemiol. 2009; 170, 173–180.Google Scholar
17. Taylor, PD, McConnell, J, Khan, IY, et al. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy. Am J Physiol. 2005; 288, R134–R139.Google Scholar
18. Samuelsson, AM, Matthews, PA, Argenton, M, et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension. 2008; 51, 383–392.Google Scholar
19. Groot, PH, van Vlijmen, BJ, Benson, GM, et al. Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure. Arterioscler Thromb Vasc Biol. 1995; 16, 926–933.Google Scholar
20. Tarling, EJ, Ryan, KJ, Bennett, AJ, Salter, AM. Effect of dietary conjugated linoleic acid isomers on lipid metabolism in hamsters fed high-carbohydrate and high-fat diets. Br J Nutr. 2009; 101, 1630–1638.Google Scholar
21. Hogan, B, Costantini, F, Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual. 1986. Cold Spring Harbor Laboratory Press: Cold Spring Habor, NY.Google Scholar
22. Paigen, B, Morrow, A, Holmes, PA, Mitchell, D, Williams, RA. Quantitative assessment of atherosclerotic lesions mice. Atherosclerosis. 1987; 68, 231–240.Google Scholar
23. Festing, MF. Design and statistical methods in studies using animal models of development. ILAR. 2006; 47, 5–14.Google Scholar
24. Erhuma, A, Bellinger, L, Langley-Evans, SC, Bennett, AJ. Prenatal exposure to undernutrition and programming of responses to high-fat feeding in the rat. Br J Nutr. 2007; 98, 517–524.Google Scholar
25. Erhuma, A, Salter, AM, Sculley, DV, Langley-Evans, SC, Bennett, AJ. Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat. Am J Physiol. 2007; 292, E1702–E1714.Google Scholar
26. Armitage, JA, Lakasing, L, Taylor, PD, et al. Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy. J Physiol. 2005; 565, 171–184.Google Scholar
27. Holemans, K, Gerber, R, O’Brien-Coker, I, et al. Raised saturated-fat intake worsens vascular function in virgin and pregnant offspring of streptozotocin-diabetic rats. Br J Nutr. 2000; 84, 285–296.Google Scholar
28. Khan, IY, Dekou, V, Douglas, G, et al. A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol. 2005; 288, R127–R133.Google Scholar
29. Khan, IY, Taylor, PD, Dekou, V, et al. Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension. 2003; 41, 168–175.Google Scholar
30. Chechi, K, Cheema, SK. Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice. Exp Clin Cardiol. 2006; 11, 129–135.Google Scholar
31. Akyol, A, McMullen, S, Langley-Evans, SC. Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet. Br J Nutr. 2012; 107, 964–978.Google Scholar
32. Napoli, C, Glass, CK, Witztum, JL, et al. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study. Lancet. 1999; 354, 1234–1241.Google Scholar
33. Palinski, W, Napoli, C. The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterol-lowering or antioxidant treatment during pregnany influence in utero programming and postnatal susceptibility to atherogenesis. FASEB J. 2002; 16, 1348–1360.Google Scholar
34. Napoli, C, de Nigris, F, Welch, JS, et al. Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation. 2002; 105, 1360–1367.Google Scholar
35. Madsen, C, Dagnaes-Hansen, F, Møller, J, Falk, E. Hypercholesterolemia in pregnant mice does not affect atherosclerosis in adult offspring. Atherosclerosis. 2003; 168, 221–228.Google Scholar
36. Goharkhay, N, Sbrana, E, Gamble, PK, et al. Characterization of a murine model of fetal programming of atherosclerosis. Am J Obstet Gynecol. 2007; 197, 416.e1– e5.Google Scholar
37. Napoli, C, D’Armiento, FP, Mancini, FP, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997; 100, 2680–2690.Google Scholar
38. Liguori, A, D’Armiento, FP, Palagiano, A, Palinski, W, Napoli, C. Maternal C-reactive protein and developmental programming of atherosclerosis. Am J Obstet Gynecol. 2008; 198, 281.e1–5.Google Scholar
39. Alkemade, FE, Gittenberger-de Groot, AC, Schiel, AE, et al. Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life. Arterioscler Thromb Vasc Biol. 2007; 27, 2228–2235.Google Scholar
40. Lillycrop, KA, Hoile, SP, Grenfell, L, Burdge, GC. DNA methylation, ageing and the influence of early life nutrition. Proc Nutr Soc. 2014; 73, 413–421.Google Scholar
41. Bogdarina, I, Haase, A, Langley-Evans, S, Clark, AJ. Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat. PLoS One. 2010; 5, e9237.Google Scholar
42. Ehara, T, Kamei, Y, Takahashi, M, et al. Role of DNA methylation in the regulation of lipogenic glycerol-3-phosphate acyltransferase 1 gene expression in the mouse neonatal liver. Diabetes. 2012; 61, 2442–2450.Google Scholar
43. Cordero, P, Gomez-Uriz, AM, Campion, J, Milagro, FI, Martinez, JA. Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet. Genes Nutr. 2013; 8, 105–113.Google Scholar
44. Grimaldi, V, Vietri, MT, Schiano, C, et al. Epigenetic reprogramming in atherosclerosis. Curr Atheroscler Rep. 2015; 17, 476.Google Scholar
45. Alkemade, FE, van Vliet, P, Henneman, P, et al. Prenatal exposure to ApoE deficiency and postnatal hypercholesterolemia are associated with altered cell-specific lysine methyltransferase and histone methylation patterns in the vasculature. Am J Pathol. 2010; 176, 542–548.Google Scholar
46. Barker, DJ, Thornburg, KL. The obstetric origins of health for a lifetime. Clin Obstet Gynecol. 2013; 56, 511–519.Google Scholar
47. Napoli, C, Witztum, JL, Calara, F, de Nigris, F, Palinski, W. Maternal hypercholesterolemia enhances atherogenesis in normocholesterolemic rabbits, which is inhibited by antioxidant or lipid-lowering intervention during pregnancy : an experimental model of atherogenic mechanisms in human fetuses. Circ Res. 2000; 87, 946–952.Google Scholar
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