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

Rubio-Aliaga, Isabel, de Roos, Baukje, Sailer, Manuela, McLoughlin, Gerard A, Boekschoten, Mark V, van Erk, Marjan, Bachmair, Eva-Maria, van Schothorst, Evert M, Keijer, Jaap, Coort, Susan L, Evelo, Chris, Gibney, Michael J, Daniel, Hannelore, Muller, Michael, Kleemann, Robert and Brennan, Lorraine (2011) Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention. Physiological Genomics, 43 (8). pp. 408-416. ISSN 1094-8341

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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.

Item Type: Article
Uncontrolled Keywords: animals,blood glucose,carbon,cholesterol,choline,dietary fats,fatty liver,hyperglycemia,insulin,insulin resistance,liver,methionine,mice,mice, inbred c57bl,obesity,triglycerides
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 21 Feb 2014 11:34
Last Modified: 23 Apr 2020 23:47
URI: https://ueaeprints.uea.ac.uk/id/eprint/47665
DOI: 10.1152/physiolgenomics.00179.2010

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