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.