Schematic presentation of the interrelationship of identified changes in gene and protein expression, as well as in metabolite levels in methyl-group donor supplemented DIO mice. (A) DIO-mediated NAFLD results in increased hepatic free fatty acid concentrations and triacylglycerol accumulation accompanied by changes of BHMT and CBS in the C1-metabolism. (B) MDS down-regulates DNL (decreased ACC1 and 2 mRNA and protein levels; not depicted) and enhances AMPK activity which induces elevated hepatic β-oxidation, thereby preventing DIO mediated NAFLD progression and further increasing BHMT expression. Observed changes of mRNA (e.g. Cpt1a), proteins (BHMT, CBS), protein phosphorylation (P-AMPKα) and metabolites (acyl-carnitine, FA) are depicted. Upward- and downward-oriented arrows indicate up-regulation or down-regulation, respectively. AMPK, AMP-activated protein kinase; C1-metabolism, one-carbon metabolism; Cpt1a, carnitine palmitoyltransferase-1a; DIO, diet-induced obesity; DMG, dimethylglycine; DNL, de novo lipogenesis; FA, free fatty acids; 5-MTHF, 5-methyl-tetrahydrofolate; NAFLD, non-alcoholic fatty liver disease; PC, phosphatidylcholine; PE, phosphatidylethanolamine; CH3, methyl group transfer via SAM; TG, triacylglycerol; THF, tetrahydrofolate; VLDL, very low density lipoprotein.