1H NMR metabonomics can differentiate the early atherogenic effect of dairy products in hyperlipidemic hamsters

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 1H 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, R2 = 0.42–0.60). NMR plasma metabonomics selectively captured part of the diet-induced metabotypes correlated with aortic cholesteryl esters (R2 = 0.63). In these metabotypes, VLDL lipids, cholesterol, and N-acetylglycoproteins (R2 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 (R2 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.