CLOCK and metabolic disease: Moreover, genome-wide gene expression studies provided the first and important insights into the role of the circadian clock in liver metabolism, and suggest that the interaction between altered energy metabolism and disruptions in the circadian clock results in a downward spiral that can cause obesity, IR, hepatic steatosis, and other metabolic diseases or exacerbate pathological states [5,6,7,8,9], though the underlying mechanisms remain largely unknown.