title: Metabolomic assessment of the effect of dietary cholesterol in the progressive development of fatty liver disease.
abstract: Nonalcoholic fatty liver disease is considered to be the hepatic manifestation of metabolic syndrome and is usually related to high-fat, high-cholesterol diets. With the rationale that the identification and quantification of metabolites in different metabolic pathways may facilitate the discovery of clinically accessible biomarkers, we report the use of (1)H NMR metabolomics for quantitative profiling of liver extracts from LDLr(-/-) mice, a well-documented mouse model of fatty liver disease. A total of 55 metabolites were identified, and multivariate analyses in a diet- and time-comparative strategy were performed. Dietary cholesterol increased the hepatic concentrations of cholesterol, triglycerides, and oleic acid but also decreased the [PUFA/MUFA] ratio as well as the relative amount of long-chain polyunsaturated fatty acids in the liver. This was also accompanied by variations of the hepatic concentration of taurine, glutathione, methionine, and carnitine. Heat-map correlation analyses demonstrated that hepatic inflammation and development of steatosis correlated with cholesterol and triglyceride NMR derived signals, respectively. We conclude that dietary cholesterol is a causal factor in the development of both liver steatosis and hepatic inflammation.
authors.affiliation: Metabolomics Platform, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), IISPV, Universitat Rovira i Virgili, Avda. Països Catalans 26, 43007 Tarragona, Spain. maria.vinaixa@urv.cat
authors.forename: Maria
authors.initials: M
authors.lastname: Vinaixa
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Rodríguez
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.forename: Raúl
authors.initials: R
authors.lastname: Beltrán
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Jesús
authors.initials: J
authors.lastname: Brezmes
authors.forename: Nicolau
authors.initials: N
authors.lastname: Cañellas
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Xavier
authors.initials: X
authors.lastname: Correig
mesh_terms: D000367:Age Factors; D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D016000:Cluster Analysis; D018450:Disease Progression; D005234:Fatty Liver / Q000378:metabolism*; D006651:Histocytochemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D018709:Statistics, Nonparametric
chemical_list: D002791:Cholesterol, Dietary; D011973:Receptors, LDL