REV-ERBα and RORs have been implicated in various diseases including metabolic diseases, immune diseases, and cancers.53,61,86,87 REV-ERBα and RORs show altered expressions and disrupted rhythms during disease development.88–90 Furthermore, alteration of REV-ERBα and RORs affects the organism susceptibility to diseases in both humans and mice and is involved in many pathways associated with pathological processes and diseases.61,87,90,91–93. This evidence concerns the gene NR1D1 and metabolic disease.