Despite the clear pathway and network differences in mouse livers after 12 weeks of LF or HF diet feeding, the initial response to a bolus of glucose is remarkably uniform and Il1a, Il1b as well as well as the transcription factors c-jun/fos (AP-1) appear to play an important role irrespectively of the degree of obesity and insulin resistance. Here, FOS is linked to obesity due to melanocortin 4 receptor deficiency.