Abnormal aortic fatty acid composition and small artery function in offspring of rats fed a high fat diet in pregnancy

Disturbances of the in utero environment are associated with an increased risk of cardiovascular disease in adulthood. In this study we have determined whether abnormal vascular function in the adult offspring of rats fed a high saturated fat diet in pregnancy is associated with altered plasma lipids or vascular fatty acid content. Female Sprague-Dawley rats were fed a breeding diet (4 % fat) or a diet high in saturated fat (20 % fat) for 10 days prior to and throughout pregnancy, and during weaning. Female offspring were then fed a maintenance diet (3 % fat) until 160 days of age. Endothelium-dependent relaxation induced by acetylcholine was blunted in isolated branches of the femoral artery from 160-day-old female offspring of dams fed the saturated fat diet when compared with female offspring of dams fed the breeding diet. These offspring exhibited elevated plasma triglyceride and reduced plasma high density lipoprotein cholesterol concentrations. The fatty acid composition of the aortas was abnormal, with a marked reduction in the content of arachidonic and docosahexaenoic acids. This study demonstrates that a high fat diet in pregnant rats produces abnormal vascular function, plasma lipid disturbances and altered vascular fatty acid content in their female offspring during adulthood. Increasing evidence suggests that disturbances of the in utero environment may ‘programme’ the fetus for development of cardiovascular disease in later life. Retrospective population studies have suggested that low birth weight is associated with an increased risk of coronary heart disease, stroke and non-insulin-dependent diabetes in adulthood (Barker, 1997). Experimentally, this association has been investigated by inducing fetal growth retardation in animals through poor nutrition. Prospective investigations of the ‘fetal programming’ hypothesis have reported hypertension in adulthood (Langley & Jackson, 1994) and disorders of glucose (Ozanne et al. 1996) and lipid metabolism (Lucas et al. 1996) in offspring of pregnant rats subjected to protein deprivation in utero. Our group has recently reported that a 30 % reduction of dietary intake in pregnant rats is associated with vascular dysfunction and hypertension in adult offspring, which were more pronounced in male animals (Ozaki et al. 2001). Fewer studies have investigated possible adverse influences on the fetus of diets more obviously associated with cardiovascular disease, but which are unrelated to growth retardation. In an earlier investigation we showed that 15- and 60-day-old offspring of rats fed saturated fat during pregnancy demonstrate vascular dysfunction and plasma lipid abnormalities (Koukkou et al. 1998), and we also reported that 1- and 15-day-old offspring exhibited profound irregularities in the fatty acid composition of the liver (Ghebremeskel et al. 1999). In the present study we have investigated vascular function in 160-day-old offspring of rats with simultaneous evaluation of parameters of lipid status. We have determined the plasma lipid profile, and because altered fatty acid composition could undermine many aspects of vascular function, have examined the composition of membrane fatty acids in the vasculature. Vascular function was assessed by measuring responses to constrictor agonists and to the endothelium-dependent vasodilator acetylcholine (ACh) in femoral arteries of offspring using a small-vessel wire myograph. Fatty acid composition was measured in aortas of offspring using thin-layer chromatography to separate the phosphoglycerides, and subsequent gas-liquid chromatography to determine individual fatty acid species.