Dose-dependent effects of dietary fat on development of obesity in relation to intestinal differential gene expression in C57BL/6J mice

Nicole J. W. de Wit, Mark V. Boekschoten, Eva-Maria Bachmair, Guido J. E. J. Hooiveld, Philip J. de Groot, Isabel Rubio-Aliaga, Hannelore Daniel, Michael Müller

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36 Citations (Scopus)


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.
Original languageEnglish
Article numbere19145
JournalPLoS One
Issue number4
Publication statusPublished - 25 Apr 2011


  • Animals
  • Dietary Fats
  • Eating
  • Gene Expression
  • Small Intestine
  • Male
  • Mice
  • Inbred C57BL Mice
  • Obesity
  • Weight Gain

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