Alterations in hepatic one-carbon metabolism and related pathways following a high fat dietary intervention

Isabel Rubio-Aliaga, Baukje De Roos, Manuela Sailer, Gerard McLoughlin, Mark van Boekschoten, Marjan van Erk, Eva Maria Bachmair, Evert van Schothorst, Jaap Keijer, Susan Coort, Chris Evelo, Michael Gibney, Hannelore Daniel, Michael Muller, Robert Kleemann, Lorraine Brennan

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51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)408-416
Number of pages9
JournalPhysiological Genomics
Volume43
Issue number8
DOIs
Publication statusPublished - Apr 2011

Keywords

  • high-fat feeding
  • obesity
  • Kennedy pathway

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    Rubio-Aliaga, I., De Roos, B., Sailer, M., McLoughlin, G., van Boekschoten, M., van Erk, M., Bachmair, E. M., van Schothorst, E., Keijer, J., Coort, S., Evelo, C., Gibney, M., Daniel, H., Muller, M., Kleemann, R., & Brennan, L. (2011). Alterations in hepatic one-carbon metabolism and related pathways following a high fat dietary intervention. Physiological Genomics, 43(8), 408-416. https://doi.org/10.1152/physiolgenomics.00179.2010