Abstract
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.
Highlights
It has been understood that dietary fats are digested in the intestinal epithelial cells, and converted to triacylglycerols (TGs)
We found that alcohol exposure stimulated adipose lipolysis and fatty acid release from white adipose tissue (WAT) [12,13]
We used an analytical method of employing high-resolution mass spectrometry in combination with metabolite deuterium labeling for the analysis of triacylglycerol
Summary
It has been understood that dietary fats are digested in the intestinal epithelial cells, and converted to triacylglycerols (TGs). TGs are assembled with apolipoproteins to form chylomicrons which are transported into the blood stream via the lymph system [1]. TGs are synthesized by the liver where they are packaged as very low-density lipoproteins (VLDL) and secreted into the blood [1]. Upon arrival in the adipose and muscle tissues, lipoprotein lipase cleaves TG into free fatty acids and glycerol. Fatty acids are taken up by these tissues, and are used as energy sources via oxidation in muscles, or re-assembled into TGs to store excess energy in the white adipose tissue (WAT) [2]. Glycerol is transported to liver or kidneys where it is converted into dihydroxyacetone phosphate by glycerol kinase and glycerol-3phosphate dehydrogenase
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