UCLA

Betaine, a methyl donor active in methionine metabolism, is effective in preventing and reversing experimental alcohol liver disease. The metabolic and molecular biologic mechanisms involved in this prevention are only partially known. To further investigate how betaine modifies the effects of ethanol on the liver, rats were given an acute ethanol bolus with or without betaine and the results were compared to isocaloric dextrose-fed controls. Livers were subjected to microarray analysis, and functional pathways and individual gene expression changes were analyzed. Experimental groups were compared by Venn diagrams showing that both ethanol and betaine caused a change in the expression of a large number of genes indicating that the changes were global. The bio-informatic analysis showed that all the KEGG functional pathways were affected and mainly down regulated at 3 h post bolus when ethanol plus betaine were compared with ethanol-fed rats. The most profound effect of betaine was on the metabolic pathways both at 3 and 12 h post bolus. At 3 h, the changes in gene expression were mostly down regulated, but at 12 h, the changes were regulated equally up and down. This hypothesis-driven analysis showed that the effects of betaine on the effects of ethanol were partly transient.