The mRNA encoding the Type II isozyme of hexokinase was markedly elevated in livers of transgenic mice overexpressing the transcriptionally active nuclear form of sterol regulatory element binding protein-1a (nSREBP-1a), but not in transgenic mice overexpressing the nSREBP-1c or nSREBP-2 isoforms. Cellulose acetate electrophoresis and immunoblotting results confirmed selective increase of the Type II isozyme in livers of transgenic mice expressing nSREBP-1a, SREBP-1a has previously been shown to activate transcription of genes encoding enzymes involved in biosynthesis of fatty acids and glycerolipids and to a lesser extent the enzymes of cholesterol biosynthesis. Thus, these results are consistent with the view that the Type II isozyme serves an anabolic function, providing precursors and reducing equivalents required for increased rates of hepatic lipid synthesis,