An Ultradian Feeding Schedule in Rats Affects Metabolic Gene Expression in Liver, Brown Adipose Tissue and Skeletal Muscle with Only Mild Effects on Circadian Clocks

Restricted feeding is well known to affect expression profiles of both clock and metabolic genes. However, it is unknown whether these changes in metabolic gene expression result from changes in the molecular clock or in feeding behavior. Here we eliminated the daily rhythm in feeding behavior by providing 6 meals evenly distributed over the light/dark-cycle. Animals on this 6-meals-a-day feeding schedule retained the normal day/night difference in physiological parameters including body temperature and locomotor activity. The daily rhythm in respiratory exchange ratio (RER), however, was significantly phase-shifted through increased utilization of carbohydrates during the light phase and increased lipid oxidation during the dark phase. This 6-meals-a-day feeding schedule did not have a major impact on the clock gene expression rhythms in the master clock, but did have mild effects on peripheral clocks. In contrast, genes involved in glucose and lipid metabolism showed differential expression. In conclusion, eliminating the daily rhythm in feeding behavior in rats does not affect the master clock and only mildly affects peripheral clocks, but disturbs metabolic rhythms in liver, skeletal muscle and brown adipose tissue in a tissue-dependent manner. Thereby, a clear daily rhythm in feeding behavior strongly regulates timing of peripheral metabolism, separately from circadian clocks.