The food-energy cellular connection revealed

"Our body's activity levels fall and rise to the beat of our internal drums—the 24-hour cycles that govern fundamental physiological functions, from sleeping and feeding patterns to the energy available to our cells. Whereas the master clock in the brain is set by light, the pacemakers in peripheral organs are set by food availability. The underlying molecular mechanism was unknown.

Now, researchers at the Salk Institute for Biological Studies shed light on the long missing connection: A metabolic master switch, which, when thrown, allows nutrients to directly alter the rhythm of peripheral clocks.

Since the body's circadian rhythm and its metabolism are closely intertwined, the risk for metabolic disease shoots up, when they are out of sync. 'Shift workers face a 100 percent increase in the risk for obesity and its consequences, such as high blood pressure, insulin resistance and an increased risk of heart attacks,' says Howard Hughes Medical Investigator Ronald M. Evans, Ph.D., a professor in the Salk Institute's Gene Expression Laboratory.

The researchers' findings, which are published in the Oct. 16, 2009, issue of Science, could have far-reaching implications, from providing a better understanding how nutrition and gene expression are linked, to creating new ways to treat obesity, diabetes and other related diseases. 'It is estimated that the activity of up to 15 percent of our genes is under the direct control of biological clocks,' says Evans. 'Our work provides a conceptual way to link nutrition and energy regulation to the genome.'...

Genetic inactivation of AMPK in mice blocks these effects, stabilizing CRY1 and severely disrupting peripheral clocks. In contrast, treating mice with AICAR, a synthetic drug that directly activates AMPK, reset the clock in cultured cells as well as in animals, confirming that cryptochromes act as energy sensors that allow to circadian clocks."