A method of employing high-resolution mass spectrometry in combination with in vivo metabolite
deuterium labeling was developed in this study to investigate the effects of alcohol exposure on
lipid homeostasis at the white adipose tissue (WAT)-liver axis in a mouse model of
alcoholic fatty liver. 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 mouse feeding experiment was performed to incorporate
deuterium into metabolites. Hepatic
lipids extracted from mouse liver, epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) were analyzed. It was found that 13 and 10
triacylglycerols (TGs) incorporated with a certain number of
deuterium were significantly increased in alcohol induced
fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of
deuterium incorporated TGs in alcohol-induced
fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of
fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in
alcoholic fatty liver.