title: Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice.
abstract: Excessive intake of dietary fat is known to be a contributing factor in the development of obesity. In this study, we determined the dose-dependent effects of dietary fat on the development of this metabolic condition with a focus on changes in gene expression in the small intestine. C57BL/6J mice were fed diets with either 10, 20, 30 or 45 energy% (E%) derived from fat for four weeks (n = 10 mice/diet). We found a significant higher weight gain in mice fed the 30E% and 45E% fat diet compared to mice on the control diet. These data indicate that the main shift towards an obese phenotype lies between a 20E% and 30E% dietary fat intake. Analysis of differential gene expression in the small intestine showed a fat-dose dependent gradient in differentially expressed genes, with the highest numbers in mice fed the 45E% fat diet. The main shift in fat-induced differential gene expression was found between the 30E% and 45E% fat diet. Furthermore, approximately 70% of the differentially expressed genes were changed in a fat-dose dependent manner. Many of these genes were involved in lipid metabolism-related processes and were already differentially expressed on a 30E% fat diet. Taken together, we conclude that up to 20E% of dietary fat, the small intestine has an effective 'buffer capacity' for fat handling. From 30E% of dietary fat, a switch towards an obese phenotype is triggered. We further speculate that especially fat-dose dependently changed lipid metabolism-related genes are involved in development of obesity.
authors.affiliation: Netherlands Nutrigenomics Centre, Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Nicole J W
authors.initials: NJ
authors.lastname: de Wit
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Bachmair
authors.forename: Guido J E J
authors.initials: GJ
authors.lastname: Hooiveld
authors.forename: Philip J
authors.initials: PJ
authors.lastname: de Groot
authors.forename: Isabel
authors.initials: I
authors.lastname: Rubio-Aliaga
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.forename: Michael
authors.initials: M
authors.lastname: Müller
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004041:Dietary Fats