Natural food intake patterns do not synchronize peripheral clocks

Food is thought to synchronize circadian clocks in the body, but this is based on time-restricted feeding (TRF) protocols. To test whether naturalistic feeding patterns are sufficient to phase-shift and entrain peripheral tissues, we measured circadian rhythms of the liver, kidney, and submandibular gland in mPer2 Luc mice under different feeding schedules. In ad lib feeding as well as in a schedule designed to mimic the ad lib pattern, PER2::LUC bioluminescence peaked during the night as expected. Surprisingly, shifting the scheduled feeding by 12h caused only small advances (<3h). To isolate the effects of feeding from the light-dark cycle, clock phase was then measured in mice acclimated to scheduled feeding and housed in constant darkness. In these conditions, peripheral clock phases were better predicted by the rest-activity cycle than the food schedule. Under natural feeding patterns, the master pacemaker in the brain sets the phase of peripheral organs independent of feeding behavior.