Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC288

Poster Communications

Effect of in utero exposure to high fat on phospholipid profiles in a mouse model of the developmental origins of cardiometabolic disease

C. R. Smith1, V. Ledger1, C. Torrens1, K. D. Bruce1, F. R. Cagampang1, C. D. Byrne1, A. D. Postle1, G. F. Clough1

1. School of Medicine, University of Southampton, Southampton, United Kingdom.

We have previously shown that in utero exposure to high fat (HF) in a mouse model primes for the later development of fatty liver and features of the metabolic syndrome (MetS) in the offspring (1). Phospholipid synthesis is essential for VLDL metabolism and membrane phospholipids are substrates for oxidation and because the MetS involves the liver and vasculature, we investigated in this mouse model how phospholipid profiles are modulated in liver and aorta by maternal and post-weaning diet and age. Female C57 Black mice were fed a high fat diet (HF; 45% kcal saturated fat, 20% kcal protein, 35% kcal carbohydrate) or standard laboratory chow diet (C; 21% kcal fat, 17% kcal protein, 63% kcal carbohydrate) before and during pregnancy and lactation. Post-weaning, offspring were maintained either on the same diet (C/C, HF/HF) or transferred to the opposite diet (C/HF, HF/C). Lipids were extracted from the liver and aorta of the male offspring at 15 and 30 weeks. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) molecular species were analysed by mass spectrometry. Data are presented as median and 95% CI (n= 3-7 animals/dietary group). The relative concentrations of liver PC species containing long chain poly-unsaturated fatty acids (LC-PUFA) increased both with age and with HF feeding, either in utero or post-weaning (repeat measures ANOVA). These effects were at the expense of decreased diunsaturated fatty acid (DUFA) species. The relative changes in PC DUFA and LC-PUFA were greatest in the HF/HF animals (DUFA: 23.5% CI=23.5-23.6; LC-PUFA: 62.1%, CI=59.2-66.8) compared to C/C (DUFA: 41.1% CI=39.1-42.3; LC-PUFA: 43.6%, CI=42.1-44.8) (p<0.001 and p<0.05, respectively). Liver PC composition of mice exposed to HF post weaning was comparable to the C/C groups at 15 weeks, but intriguingly, by 30 week was similar to that of in utero HF exposed animals. Liver PEs were unaffected by dietary HF but were modified by age. While exposure to HF (pre or post-weaning) had little effect on aortic PCs, age-related changes were apparent. We have shown, in our mouse model of human cardiometabolic disease, that exposure to HF in utero results in changes to phospholipid profile in the liver that are further modified with age. We suggest that this priming of liver PC composition may predispose to altered lipid homeostasis that may exacerbate the risk of development of cardiometabolic disease in later life. However, the absence of corresponding diet-related changes to the aortic PC compositions evidences the robust nature of homeostatic mechanisms controlling lipid profiles in vascular tissue in this mouse model.

Where applicable, experiments conform with Society ethical requirements