The cellular mechanism by which circadian rhythms – also known as the body clock – modify energy metabolism and the novel compounds that control this action have been identified by researchers at the University of California Irvine. The findings point to potential treatments for disorders triggered by circadian rhythm dysfunction, ranging from insomnia and obesity to diabetes and cancer.

“Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms,” said Paolo Sassone-Corsi, the lead researcher and the Donald Bren Professor of Biological Chemistry. “The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Disruption of these rhythms can profoundly influence human health.”

He added that up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms.

The results are detailed in two companion pieces that appeared the week of January 21 in the early online edition of the Proceedings of the National Academy of Sciences.

In one study, Sassone-Corsi and colleagues found that the biological clock controls enzymes localized in the mitochondrion, a cellular structure devoted to energy metabolism. This government occurs through acetylation of proteins, a process that operates as a switch to turn genes on and off in cells based upon the cells’ energy usage.

Some of the most important acetylation events in cells are dictated by an enzyme protein called SIRT1, which senses energy levels in the cell. Its activity is modulated by how many nutrients a cell is consuming. It also helps cells resist oxidative and radiation-induced stress. SIRT1 has been linked to the inflammatory response, diabetes and aging.

Sassone-Corsi first showed the circadian rhythm-metabolism link in 2008 and 2009, and in this study, he and his colleagues reveal the metabolic pathways through which SIRT1 works.

“When the balance between clock proteins is upset, normal cellular function can be disrupted,” said Sassone-Corsi.