Christopher VollmersScientists at the Salk Institute for Biological Studies are believed to have found that when you eat may be just as important to your health as what you eat. The findings revealed that the every day waxing and waning of thousands of genes in the liver seems to be usually controlled by food intake and not by the body’s circadian clock as conventional understanding had it. The liver is known to be the body’s metabolic clearing house.

In mammals, the circadian timing system seems to be composed of a central circadian clock in the brain and additional oscillators in most peripheral tissues. The master clock in the brain apparently is set by light. Moreover, it may be able to determine the overall diurnal or nocturnal preference of an animal together with sleep-wake cycles and feeding behavior.

“If feeding time determines the activity of a large number of genes completely independent of the circadian clock, when you eat and fast each day will have a huge impact on your metabolism,” says lead author of the study, Satchidananda (Satchin) Panda, Ph.D., an assistant professor in the Regulatory Biology Laboratory.

Also, the clocks in peripheral organs appear to be largely insensitive to changes in the light regime. Instead, their phase and amplitude could perhaps be affected by many factors including feeding time. The clocks themselves are known to keep time through the fall and increase gene activity on a roughly 24-hour schedule. This may anticipate environmental changes and adapt many of the body’s physiological function to the suitable time of day.

“The liver oscillator in particular helps the organism to adapt to a daily pattern of food availability by temporally tuning the activity of thousands of genes regulating metabolism and physiology. This regulation is very important, since the absence of a robust circadian clock predisposes the organism to various metabolic dysfunctions and diseases,” elucidates Panda.

In spite of its importance, it seems to have been unclear whether the circadian rhythms in hepatic transcription were solely controlled by the liver clock in anticipation of food or responded to actual food intake.

In order to investigate how much influence rhythmic food intake exerts over the hepatic circadian oscillator, graduate student and first author Christopher Vollmers was noted to have placed normal and clock-deficient mice on strictly controlled feeding and fasting schedules. Subsequently, he appeared to have monitored gene expression across the whole genome.

The findings showed that putting mice on a strict 8-hour feeding or 16-hour fasting schedule seemed to have restored the circadian transcription pattern of nearly all metabolic genes inside the liver of mice without a circadian clock. On the contrary, during prolonged fasting, only a small subset of genes was observed to have continued to be transcribed in a circadian pattern even with a functional circadian clock present.

“Our study represents a seminal shift in how we think about circadian cycles. The circadian clock is no longer the sole driver of rhythms in gene function, instead the phase and amplitude of rhythmic gene function in the liver is determined by feeding and fasting periods—the more defined they are, the more robust the oscillations becomes,” says Panda.

The significance of robust metabolic rhythms for our health appears to have been established via shift workers’ increased risk of developing metabolic syndrome. However, the fundamental molecular reasons still seem to be unclear.

Panda was of the opinion that the oscillations may serve one big purpose to separate incompatible processes. These processes include the generation of DNA-damaging reactive oxygen species and DNA replication. The findings of the study may perhaps explain why shift workers are strangely prone to metabolic syndrome, diabetes, high cholesterol levels and obesity.

The findings of the study will be published in a forthcoming issue of the Proceedings of the National Academy of Sciences.