title: Multilevel systems biology modeling characterized the atheroprotective efficiencies of modified dairy fats in a hamster model.
abstract: We assessed the atheroprotective efficiency of modified dairy fats in hyperlipidemic hamsters. A systems biology approach was implemented to reveal and quantify the dietary fat-related components of the disease. Three modified dairy fats (40% energy) were prepared from regular butter by mixing with a plant oil mixture, by removing cholesterol alone, or by removing cholesterol in combination with reducing saturated fatty acids. A plant oil mixture and a regular butter were used as control diets. The atherosclerosis severity (aortic cholesteryl-ester level) was higher in the regular butter-fed hamsters than in the other four groups (P < 0.05). Eighty-seven of the 1,666 variables measured from multiplatform analysis were found to be strongly associated with the disease. When aggregated into 10 biological clusters combined into a multivariate predictive equation, these 87 variables explained 81% of the disease variability. The biological cluster "regulation of lipid transport and metabolism" appeared central to atherogenic development relative to diets. The "vitamin E metabolism" cluster was the main driver of atheroprotection with the best performing transformed dairy fat. Under conditions that promote atherosclerosis, the impact of dairy fats on atherogenesis could be greatly ameliorated by technological modifications. Our modeling approach allowed for identifying and quantifying the contribution of complex factors to atherogenic development in each dietary setup.
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France; jean-charles.martin@univ-amu.fr.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Martin
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Amélie
authors.initials: A
authors.lastname: Berton
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Christian
authors.initials: C
authors.lastname: Ginies
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Romain
authors.initials: R
authors.lastname: Bott
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Scheercousse
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Alessandra
authors.initials: A
authors.lastname: Saddi
authors.affiliation: UMR 8195 Centre de Neurosciences Paris-Sud, Neuroendocrinologie Moléculaire de la Prise Alimentaire, Université Paris-Sud XI, Orsay, France; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gripois
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
authors.affiliation: Corman, S.A., Goé, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dalemans
authors.affiliation: INRA UMR1260, Nutrition, Obésité et Risque Thrombotique, Marseille, France; Aix-Marseille Université, Faculté de Médecine, Marseille, France; and INSERM, UMR1062, Nutrition, Obésité et Risque Thrombotique, Marseille, France;
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.affiliation: UMR 8195 Centre de Neurosciences Paris-Sud, Neuroendocrinologie Moléculaire de la Prise Alimentaire, Université Paris-Sud XI, Orsay, France; and.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Delplanque
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000517:prevention & control*; D006224:Cricetinae; D003611:Dairy Products; D004041:Dietary Fats / Q000032:analysis / Q000627:therapeutic use*; D008297:Male; D008647:Mesocricetus; D008955:Models, Cardiovascular; D049490:Systems Biology; D014810:Vitamin E / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D014810:Vitamin E
keywords: atherosclerosis; cholesterol; dairy fats; metabolomics; systems biology