Rapid damping of food-entrained circadian rhythm of clock gene expression in clock-defective peripheral tissues under fasting conditions

Restricted feeding-induced free-running oscillation of clock genes in the liver was studied in homozygous Clock-mutant (Clock/Clock) mice. Similar to wild-type mice, Clock/Clock mice showed robust food-anticipatory behavioral activity in accordance with a restricted feeding schedule. Also, the peak of all clock gene mRNAs tested was phase-advanced in the liver of Clock/Clock mice as well as wild-type mice, although the amplitude of clock gene expression was low in Clock/Clock mice. The food-anticipatory behavioral rhythm in Clock/Clock mice maintained a period similar to wild-type mice during 2-day fasting after the cessation of restricted feeding. However, during the fasting days after temporal feeding cues were removed, the oscillation of clock genes in the liver and heart, excluding the suprachiasmatic nuclei, appeared to result in arrhythmicity in Clock/Clock mice. Thus, although the CLOCK-based molecular mechanism is not required for the expression of food-anticipatory activity, intact CLOCK protein might be involved in sustaining several cycles of peripheral circadian oscillations after restricted feeding-induced resetting.