Fig. 1.

The molecular circadian clock system and hepatic clock gene rhythms. A: the molecular circadian clock mechanism comprises transcriptional-translational feedback loops that control 24-h rhythms in clock genes and numerous other clock-controlled genes. At the core of the clock mechanism is the BMAL1-CLOCK heterodimer that activates transcription of multiple clock genes including components that comprise the negative feedback loops (PER, CRY, and REV-ERB), the positive feedback loop (ROR), and the transcription factors that regulate Bmal1 expression (ROR and REV-ERB). These feedback loops also regulate transcription of numerous non-clock metabolic genes. B: diurnal oscillations of Bmal1, Per2, and Dbp mRNA levels in livers from wild-type C57BL/6J male mice fed a normal chow diet. Livers were collected every 4 h [Zeitgeber time (ZT) 0 = lights on, ZT 12 = lights off]. Data significantly fit to a cosine function and represent the means ± SE for n = 4–6 mice per time point.