Heart and liver have rhythm

Organ clocks orchestrate physiology.

Your body may feel in tune but your organs are doing their own thing. Our hearts and livers follow their own daily routines, say Boston researchers.

The brain carries a central circadian clock whose activity has a 24-hour cycle. Like town clocks set by the Greenwich tones, the body’s organs run secondary timekeepers. These coordinate regular activities such as metabolism, digestion and blood pressure.

The chiming of each organ clock triggers different waves of gene activity, Charles Weitz and his team now show¹. In liver and heart, different sets of genes cycle in a 24-hour phase, they found, with peaks and troughs at different times.

„It shows that different tissues have to be cycling for different reasons,“ says Ueli Schibler of the University of Geneva in Switzerland. This allows organs to reset their activities according to their own priorities. „It makes a lot of sense,“ Schibler says.

„Feeding time appears to be the strongest synchronizer,“ he says. Shifting a mouse’s mealtimes from night to day resets the activity cycles of genes in peripheral organs, he has found; the brain’s clock is unaffected. This allows the appropriate organs to gear up for food processing in anticipation of meals, similar to how a night-shift worker might readjust.

Alcohol, for example, is detoxified most efficiently between 5 and 6 in the evening – in time for the first gin and tonic. „A lot of people are beginning to recognize that the timing of taking drugs is critically important,“ says Michael Menaker, who studies circadian rhythms at the University of Virginia in Charlottesville. Studies such as Weitz’s will fuel this emerging field of ’chronopharmacology’, he predicts.

Clock watching

Weitz, of Harvard Medical School, and his team compared more than 12,000 genes active in liver and heart over two days while mice were exposed to constant light. Between 8 and 10% of genes in each tissue varied their activity following the 24-hour cycle, they found – a measure of the large influence of time on the body.

But few of the genes cycling in the heart were also cycling in the liver. And although heart genes tend to peak synchronously, liver genes peak through morning, noon and night.

Weitz took a crude look at what these genes do. He found that, despite their dissimilarity, they span a similar range of functions in each tissue, including cell communication, metabolism and transport.

The central clock, meanwhile, keeps the other clocks ticking in time. „They’re marching to a drum beaten by the brain,“ says Weitz, „but peripheral clocks can step out and do their own thing.“

How the central clock sends signals to its followers remains unknown – but this study may identify some candidates, says Menaker.

References

1. Storch, K-F. Extensive and divergenet circadian gene expression in liver and heart. Nature, advanced online publication, doi:10.1038/nature744 (2002).