Even though our data are insufficient to make a direct link between hepatocyte p110α and downstream SREBP1-c in the regulation of HFD-induced liver gene rhythmicity, we have highlighted the critical role of insulin-driven p110α signaling in the regulation of SREBP1-c, especially during HFD-induced obesity. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.