They said that the findings can lead to new approaches to treating disorders such as metabolic syndrome that can result, at least in part, from chronic disruption of the sleep-wake cycle.
"People knew that the clock regulates many different processes, but what they didn't realize what that when you tweak those processes, it feeds back and alters the clock," said Steve Kay, Dean of the Division of Biological Sciences at the University of California, San Diego, who led the study along with John Hogenesch of the University of Pennsylvania.
A molecular clock controls daily physiological rhythms in many types of cells, even cells grown in culture.
By engineering cultured cells to glow yellow when a particular clock gene switched on, the team made the cycle visible. They then interfered with every human gene to see which would shift the clock. They found that hundreds altered the timing.
"We just suddenly discovered 350 new genes that affect the clock that weren't known before," Kay said.
However, subsequent screening to confirm the genes' effect on a second clock gene narrowed the list to 200.
Seven genes involved in insulin control also influenced the rhythms of the clock.
"What came out very strongly was this close relationship between circadian regulation and insulin signalling. There's a reciprocal relationship between circadian dysfunction and metabolic dysfunction," said Kay.
The researchers suggest that genetically altered mice with malfunctioning clocks become obese and develop diet-induced diabetes.Understanding this close relationship between circadian regulation and metabolic homeostasis should provide novel ways of identifying new therapies for metabolic disease," Kay added.
The study appears in journal Cell.