title: Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention.
abstract: Obesity frequently leads to insulin resistance and the development of hepatic steatosis. To characterize the molecular changes that promote hepatic steatosis, transcriptomics, proteomics, and metabolomics technologies were applied to liver samples from C57BL/6J mice obtained from two independent intervention trials. After 12 wk of high-fat feeding the animals became obese, hyperglycemic, and insulin resistant, had elevated levels of blood cholesterol and VLDL, and developed hepatic steatosis. Nutrigenomic analysis revealed alterations of key metabolites and enzyme transcript levels of hepatic one-carbon metabolism and related pathways. The hepatic oxidative capacity and the lipid milieu were significantly altered, which may play a key role in the development of insulin resistance. Additionally, high choline levels were observed after the high-fat diet. Previous studies have linked choline levels with insulin resistance and hepatic steatosis in conjunction with changes of certain metabolites and enzyme levels of one-carbon metabolism. The present results suggest that the coupling of high levels of choline and low levels of methionine plays an important role in the development of insulin resistance and liver steatosis. In conclusion, the complexities of the alterations induced by high-fat feeding are multifactorial, indicating that the interplay between several metabolic pathways is responsible for the pathological consequences.
authors.affiliation: Molecular Nutrition Unit, ZIEL-Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rubio-Aliaga
authors.forename: Baukje de
authors.initials: Bd
authors.lastname: Roos
authors.forename: Manuela
authors.initials: M
authors.lastname: Sailer
authors.forename: Gerard A
authors.initials: GA
authors.lastname: McLoughlin
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.forename: Marjan
authors.initials: M
authors.lastname: van Erk
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Bachmair
authors.forename: Evert M
authors.initials: EM
authors.lastname: van Schothorst
authors.forename: Jaap
authors.initials: J
authors.lastname: Keijer
authors.forename: Susan L
authors.initials: SL
authors.lastname: Coort
authors.forename: Chris
authors.initials: C
authors.lastname: Evelo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gibney
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.forename: Michael
authors.initials: M
authors.lastname: Muller
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002794:Choline / Q000378:metabolism*; D004041:Dietary Fats; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008715:Methionine / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D014280:Triglycerides; D002244:Carbon; D002784:Cholesterol; D008715:Methionine; D002794:Choline