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

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 18A c c e p t e d M a n u s c r i p t Diet is an important environmental factor modulating the onset of atherosclerosis. The 2 aim of this study was to evaluate the effects of different dairy-based food products on early 3 atherogenesis using both conventional and metabonomic approaches in hyperlipidemic 4 hamsters. The hamsters received up to 200 g/kg of fat as anhydrous butter or cheese made 5 from various milk fats or canola-based oil (CV), in addition to a non-atherogenic low-fat diet. 6Aortic cholesteryl ester loading was considered to be an early atherogenic point, and 7 metabolic changes linked to atherogenesis were measured using plasma 1 H-NMR-based 8 metabonomics. The lowest atherogenicity was obtained with the plant-oil cheese diet, 9followed by the dairy fat cheese diet, while the greatest atherogenicity was observed with the 10 butter diet (P < 0.05). Disease outcome was correlated with conventional plasma biomarkers 11 (total cholesterol, triglycerides, LDL cholesterol, R 2 =0.42-0.60). NMR plasma metabonomics 12 selectively captured part of the diet-induced metabotypes correlated with aortic cholesteryl 13 esters (R 2 =0.63). In these metabotypes, VLDL lipids, cholesterol, and N-acetylglycoproteins 14 (R 2 range: 0.45-0.51) were the most positively correlated metabolites, whereas a 15 multimetabolite response at 3.75ppm, albumin lysyl residues, and trimethylamine-N-oxide 16were the most negatively correlated metabolites (R 2 range: 0.43-0.63) of the aortic cholesteryl 17 esters. Collectively, these metabolites predicted 89% of atherogenic variability compared to 18 the 60% predicted by total plasma cholesterol alone. In conclusion, we show that the food 19 environment can modulate the atherogenic effect of dairy fat. This proof-of-principle study 20demonstrates the first use of plasma metabonomics for improving the prognosis of diet-21 induced atherogenesis, revealing novel potential disease biomarkers. 22Keywords: nuclear magnetic resonance spectroscopy, milk fat, atherosclerosis biomarkers, 23 hamster, metabonomics 24 25

The protective effect of processed cheese against hyperlipidemia in rats

“…Also, neither raw nor retrograded resistant starch had any significant effect on the serum lipids of healthy subjects [15]. Martin et al [23] indicated that the determinal effect of a high saturated intake on atherogenesis can be modulated by accompanying compounds or the physico-chemical nature of the food matrix. This may be considered as another factor responsible for the observed differences in the atherogenic effects of the different processed cheeses tested.…”

“…The long chain ω-3 fatty acids are known by their protective effect on the CVD [26]. Recently, a study based on conventional and metabonomic approaches showed that the lowest atherogenicity was obtained with canola cheese diet followed by the dairy fat cheese diet, while the greatest atherogenicity was observed with the butter diet (P < 0.05) in hyperlipidemic hamsters [23]. Also, in the controlled dietary study on human subjects [3,29], cheese was less cholesterol increasing than butter at equal fat content.…”

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders

“…Exclusion criteria were as follows: a history of head injury with a loss of consciousness .30 min; a substantial physical (e.g., uncorrected visual impairment or hemiparesis), neurologic (e.g., seizure disorder), or psychiatric (e.g., active psychosis) disability that precluded involvement in the study; evidence of any other known causes of mental deficiency (e.g., congenital hypothyroidism, neurofibromatosis, or chromosomal abnormalities); or the prescription of medications that were suggestive of or might increase risk of atherosclerosis (e.g., b blockers, hormone supplements, protease inhibitors, and long-term systemic prednisone and cyclosporine) because of a remote associative risk of choline metabolite trimethylamine-N-oxide with atherosclerotic heart disease in cardiac patients (20)(21)(22)(23)(24). Medication changes during the treatment period did not preclude study participation but were monitored.…”

Interindividual variability of lutein bioavailability in healthy men: characterization, genetic variants involved, and relation with fasting plasma lutein concentration

“…The model that maximized the explained variance (R 2 ) and predicted variance (Q 2 ) and validated the following crossvalidation ANOVA was selected. See Supplementary Methods under "Supplemental data" in the online issue for additional validation procedures of PLS regression models (41,42) that were also performed. SIMCA-P12 software (Umetrics) was used for all multivariate data analyses and modeling.…”