This may explain why “night-work” results in diseases associated with metabolic disorders such as obesity and diabetes by down regulating metabolic genes such as Nampt, Sirt1, Pgc-1α and Pparα. This highlights the complexity of the interaction between the circadian system and metabolism, and poses a daunting challenge to understand the circadian metabolic network that has been shown in the present study to be so extremely vulnerable for a temporal disturbance in the balance of its components. This evidence concerns the gene PPARGC1A and obesity due to melanocortin 4 receptor deficiency.