Irvine, Calif., Dec. 19, 2013 — A high-fat diet affects the molecular mechanism controlling the internal body clock that regulates metabolic functions in the liver, UC Irvine scientists have found. Disruption of these circadian rhythms may contribute to metabolic distress ailments, such as diabetes, obesity and high blood pressure.
There's good news, though. The researchers also discovered that returning to a balanced, low-fat diet normalized the rhythms. This study reveals that the circadian clock is able to reprogram itself depending on a diet's nutritional content – which could lead to the identification of novel pharmacological targets for controlled diets.
UC Irvine's Paolo Sassone-Corsi, the Donald Bren Professor of Biological Chemistry and one of the world's leading researchers on the genetics of circadian rhythms, led the study, which appears in Cell.
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, including those involved with metabolic pathways in the liver.
A high-fat diet reprograms the liver clock through two main mechanisms. One blocks normal cycles by impeding the clock regulator genes called CLOCK:BMAL1. The other initiates a new program of oscillations by activating genes that normally do not oscillate, principally through a factor called PPAR-gamma. Previously implicated in inflammatory responses and the formation of fatty tissue, this factor oscillates with a high-fat diet.
It's noteworthy, Sassone-Corsi said, that this reprogramming takes place independent of the state of obesity; rather, it's solely dependent upon caloric intake – showing the remarkable adaptability of the circadian clock.
The authors will extend their research to the effects of a high-fat diet on other body components, including muscle, fat, the brain and blood plasma.
Pierre Baldi, Kristin Eckel-Mahan, Vishal Patel, Sara de Mateo Lopez, Ricardo Orozco Solis, Nicholas Ceglia, Saurabh Sahar and Sherry Dilag-Penilla of UC Irvine; and Kenneth Dyar of the Venetian Institute of Molecular Medicine in Padova, Italy, contributed to the study, which received support from the National Institutes of Health (grants F32 DK083881, GM081634, AG033888, LM010235 and T15 LM07443), the National Science Foundation, the Merieux Research Institute and Sirtris/GSK.
About the University of California, Irvine: Located in coastal Orange County, near a thriving employment hub in one of the nation's safest cities, UC Irvine was founded in 1965. One of only 62 members of the Association of American Universities, it's ranked first among U.S. universities under 50 years old by the London-based Times Higher Education. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Michael Drake since 2005, UC Irvine has more than 28,000 students and offers 192 degree programs. It's Orange County's second-largest employer, contributing $4.3 billion annually to the local economy.
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