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Strict Genomic Partitioning by Biological Clock Separates Key Metabolic Functions
Much of the liver’s metabolic function is governed by circadian rhythms – our own body clock – and UC Irvine (UCI) researchers have now found two independent mechanisms by which this occurs. The study, published online today July 31, 2014 in Cell, reveals new information about the body clock’s sway over metabolism and points the way to more focused drug treatments for liver disease and such metabolic disorders as obesity and diabetes. Dr. Paolo Sassone-Corsi, UCI’s Donald Bren Professor of Biological Chemistry, and postdoctoral scholar Dr. Selma Masri report that two of these circadian-linked proteins, SIRT1 and SIRT6, manage important liver processes – lipid storage and energy usage in liver cells – separately and distinctly from each other. This surprising discovery of genomic partitioning, Dr. Masri noted, reveals how strictly regulated circadian control of metabolism can be. “The ability of the genome and epigenome to cross-talk with metabolic pathways is critical for cellular and organismal functions. What’s remarkable is that the circadian clock is intimately involved in this dialogue,” she said. Circadian rhythms of 24 hours govern fundamental physiological functions in virtually all organisms. The circadian clocks are intrinsic time-tracking systems in our bodies that anticipate environmental changes and adapt themselves to the appropriate time of day. Changes to these rhythms can profoundly influence human health. Up to 15 percent of people’s genes are regulated by the day-night pattern of circadian rhythms; nearly 50 percent of those involved with metabolic pathways in the liver are influenced by these rhythms.