ABSTRACT
Diet is an important environmental factor modulating the onset of atherosclerosis. The aim of this study was to evaluate the effects of different dairy-based food products on early atherogenesis using both conventional and metabonomic approaches in hyperlipidemic hamsters. The hamsters received up to 200 g/kg of fat as anhydrous butter or cheese made from various milk fats or canola-based oil (CV), in addition to a non-atherogenic low-fat diet. Aortic cholesteryl ester loading was considered to be an early atherogenic point, and metabolic changes linked to atherogenesis were measured using plasma (1)H NMR-based metabonomics. The lowest atherogenicity was obtained with the plant-oil cheese diet, followed by the dairy fat cheese diet, while the greatest atherogenicity was observed with the butter diet (P<0.05). Disease outcome was correlated with conventional plasma biomarkers (total cholesterol, triglycerides, LDL cholesterol, R(2)=0.42-0.60). NMR plasma metabonomics selectively captured part of the diet-induced metabotypes correlated with aortic cholesteryl esters (R(2)=0.63). In these metabotypes, VLDL lipids, cholesterol, and N-acetylglycoproteins (R(2) range: 0.45-0.51) were the most positively correlated metabolites, whereas a multimetabolite response at 3.75 ppm, albumin lysyl residues, and trimethylamine-N-oxide were the most negatively correlated metabolites (R(2) range: 0.43-0.63) of the aortic cholesteryl esters. Collectively, these metabolites predicted 89% of atherogenic variability compared to the 60% predicted by total plasma cholesterol alone. In conclusion, we show that the food environment can modulate the atherogenic effect of dairy fat. This proof-of-principle study demonstrates the first use of plasma metabonomics for improving the prognosis of diet-induced atherogenesis, revealing novel potential disease biomarkers.