Metabolomics Analysis Reveals Reverse Fatty Acid Transport in Alcoholic Fatty Liver

摘要

A high-resolution mass spectrometry-based metabolomics approach was employed to prove the hypothesis of reverse fatty acid transport in alcohol induced fatty liver, i.e., alcohol consumption may stimulate lipolysis in adipose tissue, leading to a significant release of fatty acids, which are transported back and deposited into the liver for the synthesis of triacylglycerides. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver were analyzed using FT-MS and LTQ-MS/MS via direct infusion for lipid quantification and identification. Time course trajectories of 747 metabolites were generated in this study, with Pearson's correlation coefficients ranging from 0.8 to 1.0 and Fisher's combined probability values ranging from 8.8 to 28.9.. It was discovered that 15 and 14 triacylglycerides were significantly up-regulated at time points 2 weeks and 4 weeks in the alcohol induced fatty liver, respectively. The significant up-regulation of deuterium labeled triacylglyerides in alcohol induced fatty liver proves the hypothesis of reverse fatty acid transport.