A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring

1 Maternal and Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, King's College, London; and 2 Centre for the Developmental Origins of Health and Disease, Princess Anne Hospital, Southampton, United Kingdom Submitted 1 June 2004 ; accepted in final form 31 July 2004 Epidemiological and animal studies suggest that diet-induced epigenetic modifications in early life can contribute to development of the metabolic syndrome in adulthood. We previously reported features of the metabolic syndrome in adult offspring of rats fed a diet rich in animal fat during pregnancy and suckling. We now report a study to compare the relative effects of high-fat feeding during 1 ) pregnancy and 2 ) the suckling period in the development of these disorders. As observed previously, 6-mo-old female offspring of fat-fed dams suckled by the same fat-fed dams (OHF) demonstrated raised blood pressure, despite being fed a balanced diet from weaning. Female offspring of fat-fed dams "cross fostered" to dams consuming a control diet during suckling (OHF/C) demonstrated raised blood pressure compared with controls (OC) [systolic blood pressure (SBP; mmHg) means ± SE: OHF/C, 132.5 ± 3.0, n = 6 vs. OC, 119.0 ± 3.8, n = 7, P < 0.05]. Female offspring of controls cross fostered to dams consuming the fat diet (OC/HF) were also hypertensive [SBP (mmHg) 131.0 ± 2.5 mmHg, n = 6 vs. OC, P < 0.05]. Endothelium-dependent relaxation (EDR) of male and female OHF and OHF/C mesenteric small arteries was similar and blunted compared with OC ( P < 0.001). OC/HF arteries showed profoundly impaired EDR (OC/HF vs. OHF, P < 0.001). OHF/C and OC/HF demonstrated hyperinsulinemia and increased adiposity. Features of the metabolic syndrome in adult offspring of fat-fed rats can be acquired both antenatally and during suckling. However, exposure during pregnancy confers adaptive protection against endothelial dysfunction induced by maternal fat feeding during suckling. blood pressure; endothelium; developmental programming Address for reprint requests and other correspondence: P. D. Taylor, Division of Reproductive Health, Endocrinology and Development, St. Thomas' Hospital, London SE1 7EH, UK (E-mail: paul.taylor{at}kcl.ac.uk )