(V O2), and respiratory quotient (RQ) in mice were monitored continuously throughout 12:12-h light-dark cycles before, during, and after time-restricted feeding (RF). Mice fed ad libitum showed robust daily rhythms in both parameters: high during the dark phase and low during the light phase. The daily profile of energy metabolism in mice under daytime-only feeding was reversed at the beginning of the first fasting night. A few days after daytimeonly feeding began, RF also reversed the circadian core body temperature rhythm. Moreover, RF for 6 consecutive days shifted the phases of circadian expression patterns of clock genes in liver significantly by 8 -10 h. When mice were fed a high-fat (HF) diet ad libitum, the daily rhythm of RQ dampened day by day and disappeared on the sixth day of RF, whereas V O2 showed a robust daily rhythm. Mice fed HF only in the daytime had reversed V O2 and RQ rhythms. Similarly, mice fed HF only in the daytime significantly phase shifted the clock gene expression in liver, whereas ad libitum feeding with HF had no significant effect on the expression phases of liver clock genes. These results suggested that V O2 is a sensitive indicator of entrainment in the mouse liver. Moreover, physiologically, it can be determined without any surgery or constraint. On the basis of these results, we hypothesize that a change in the daily V O2 rhythm, independent of the energy source, might drive phase shifts of circadian oscillators in peripheral tissues, at least in the liver. circadian rhythm; metabolic rate; respiratory quotient; fat; core body temperature MOST LIVING ORGANISMS EXHIBIT a variety of daily rhythms in physiology and behavior, such as energy metabolism, body temperature, sleep, and wakefulness (4, 30). Endogenous oscillators not only control these rhythmic phenomena but also play important roles in adaptability to sudden changes in living environments (9,29). In mammals, the suprachiasmatic nucleus (SCN) is identified as the center of master pacemakers and can drive autonomic oscillation without any environmental time information (4, 13, 37). The SCN can also receive information about environmental light through the retinohypothalamic tract from the eyes to entrain the biological rhythm to the environmental light-dark cycle. Therefore, light is considered the most effective external time cue.Time of food access is a time cue (20, 32) that entrains peripheral oscillators, called food-entrainable oscillators (FEO). When rodents were restricted to eating only during light-rest periods, they exhibited food-anticipatory activity (FAA) before daily food presentation (6, 19). The restricted feeding (RF) of mice for several days shifted the phases of the circadian rhythm of clock gene expression in peripheral tissues even under cyclic light-dark conditions without affecting the phases of central oscillators in the SCN (5,12,33,36). These lines of evidence indicate that food metabolites or signals (neuronal and/or humoral) elicited by food processing would be the principal timing cues f...
