Figure 3: RORα and RORγ function as intermediaries between the circadian clock and its regulation of glucose/lipid metabolic and inflammatory gene expression. RORs are linked to the circadian clock at different levels: a) ROR expression is regulated by the circadian clock machinery, including Bmal1, Clock, Rev-Erbs and Cry1; b) RORs are involved in the modulation of clock gene expression, including Npas2, Clock and Rev-Erb, and participate in the regulation of the rhythmic expression of glucose and lipid metabolic genes as well as inflammatory genes; c) Deficiency in RORα or RORβ causes changes in the circadian behavior, which might be linked to neuropsychiatric disorders, while deficiency in RORγ leads to increased insulin sensitivity and glucose tolerance and a lower risk of developing diabetes.