TY - JOUR
T1 - Alterations in hepatic one-carbon metabolism and related pathways following a high fat dietary intervention
AU - Rubio-Aliaga, Isabel
AU - De Roos, Baukje
AU - Sailer, Manuela
AU - McLoughlin, Gerard
AU - van Boekschoten, Mark
AU - van Erk, Marjan
AU - Bachmair, Eva Maria
AU - van Schothorst, Evert
AU - Keijer, Jaap
AU - Coort, Susan
AU - Evelo, Chris
AU - Gibney, Michael
AU - Daniel, Hannelore
AU - Muller, Michael
AU - Kleemann, Robert
AU - Brennan, Lorraine
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
KW - high-fat feeding
KW - obesity
KW - Kennedy pathway
U2 - 10.1152/physiolgenomics.00179.2010
DO - 10.1152/physiolgenomics.00179.2010
M3 - Article
SN - 1094-8341
VL - 43
SP - 408
EP - 416
JO - Physiological Genomics
JF - Physiological Genomics
IS - 8
ER -