November 25, 2009
LA JOLLA, Calif.The time period one eats and fasts each day controls metabolism says new research from the Salk Institute for Biological Studies. The new mouse study, to be published in a forthcoming issue of the Proceedings of the National Academy of Sciences, revealed the daily waxing and waning of thousands of genes in the liverthe body's metabolic clearinghouseis mostly controlled by food intake and not by the body's circadian clock as conventional wisdom had it.
In mammals, the circadian timing system is composed of a central circadian clock in the brain and subsidiary oscillators in most peripheral tissues. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior. The clocks in peripheral organs are largely insensitive to changes in the light regime. Instead, their phase and amplitude are affected by many factors including feeding time. The clocks themselves keep time through the fall and rise of gene activity on a roughly 24-hour schedule that anticipates environmental changes and adapts many of the body's physiological function to the appropriate time of day.
To investigate how much influence rhythmic food intake exerts over the liver circadian oscillator, graduate student and first author Christopher Vollmers put normal and clock-deficient mice on strictly controlled feeding and fasting schedules while monitoring gene expression across the whole genome. He found putting mice on a strict eight-hour feeding/16-hour fasting schedule restored the circadian transcription pattern of most metabolic genes in the liver of mice without a circadian clock. Conversely, during prolonged fasting, only a small subset of genes continued to be transcribed in a circadian pattern even with a functional circadian clock present.
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