FIG. 6.
A novel metabolic regulatory network predicted by integration of genomic, transcriptomic, and metabolomic profiling. Whole-genome mapping was integrated with transcriptomic and metabolomic analysis of liver samples in F2 mice from a cross of diabetes-resistant B6-ob/ob mice and diabetes-susceptible BTBR-ob/ob mice. Networks of transcripts (grey ovals) and metabolites (rectangle) were identified by computational analysis (63). The network shown here predicts that the amino acid glutamate/glutamine (Glx) regulates expression of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase (Pck1) via regulation of alanine/glyoxylate aminotransferase (Agxt) and arginase1 (Arg1). Consistent with this prediction, glutamine addition to mouse hepatocytes strongly induces expression of Agxt, Arg1, and Pck1 (20). Figure reproduced with permission from ref. 19.