CLOCK and metabolic disease: In addition to clock genes, our previous study [58] and other research [67] showed that adverse early-life nutritional challenges programed metabolic diseases in later life; in the meantime, clock-control genes were significantly disrupted, such as PPARα, inositol-requiring 1 alpha (IRE1α), protein kinase RNA (PKR)-like ER kinase (PERK),and activating transcription factor 6 (ATF6) in the endoplasmic reticulum stress-associated unfolded protein response (UPR) signaling pathways, of which the expressions are rhythmic and play a key role in the link between circadian rhythm and metabolism.