A high fat diet leads to hypercholesterolemia and predisposes the individual to developing cardiovascular disease (CVD). We hypothesised that the mother’s diet before and during pregnancy and lactation can also influence predisposition to CVD in offspring fed a hypercholesterolemic diet. We therefore examined the effects of feeding a high fat-high cholesterol diet on cardiovascular function in female mouse offspring from mothers fed a hypercholesterolemic diet during pregnancy and lactation. Female C57BL/6 mice were fed either a high fat-high cholesterol diet (HF; 45% kcal fat) or standard chow (C; 21% kcal fat) from weaning through pregnancy and lactation. Weaned female offspring from each group were then fed either a HF or C diets to adulthood. Body weight, blood pressure, plasma cholesterol and C-reactive protein levels (a marker of CVD) were measured at 36 weeks post-weaning. Histology of the liver was also performed. Data were expressed as mean ± SEM and analysed by ANOVA followed by post-hoc test. At 36 weeks post weaning the offspring from high fat fed mothers that were then fed a high fat diet (HF-HF) or a chow diet (HF-C), and offspring from chow fed mothers fed a high fat diet (C-HF) had significantly elevated bodyweight (gm; HF-HF 34.7±0.3; C-HF 34.6±0.4; HF-C 29.6±0.2 vs. C-C 20.6±0.1; p<0.001), systolic BP (mmHg; HF-HF 139±0.1; C-HF 151.6±2.0; HF-C 146.2±2.3 vs. C-C 104.7±0.1; p<0.001), plasma cholesterol (mml/L; HF-HF 3.2± 0.4; C-HF 3.0± 0.3; HF-C 2.7±0.2 vs. C-C 1.8±0.1; p<0.001) and plasma CRP levels (mml/L; HF-HF 11.9±0.2; C-HF 12.8±0.4 vs. C-C 3.8±0.1; p<0.001) compared to C-C offspring. Liver histology also showed lipid vacuoles within hepatocytes in the HF-HF, HF-C & C-HF but not the C-C offspring. We conclude that as expected feeding a HF diet induces CVD risk factors. For blood pressure feeding the dam a HF diet was not protective, as previously reported in a rat model (Khan et al. 2004). Interestingly, blood pressure and cholesterol were also elevated in offspring of the HF-fed dams even when fed C. Our results may have implications for understanding the effects of the ‘nutritional transition’ to higher dietary intake of energy and fat which lead to increased cardiovascular disease in many societies. Acknowledgements: Supported by BUPA, HOPE and BHFReference 1 : Khan I et al. (2004) Circulation 110, 1097-1102