In a University of California, Irvine-led study, researchers found evidence that fasting affects circadian clocks in the liver and skeletal muscle, causing them to rewire their metabolism, which can ultimately lead to improved health and protection against aging-associated diseases. The study was published recently in Cell Reports.
The circadian clock operates within the body and its organs as intrinsic time-keeping machinery to preserve homeostasis in response to the changing environment. And, while food is known to influence clocks in peripheral tissues, it was unclear, until now, how the lack of food influences clock function and ultimately affects the body.
"We discovered fasting influences the circadian clock and fasting-driven cellular responses, which together work to achieve fasting-specific temporal gene regulation," said lead author Paolo Sassone-Corsi, Donald Bren Professor of Biological Chemistry at UCI's School of Medicine. "Skeletal muscle, for example, appears to be twice as responsive to fasting as the liver."
The research was conducted using mice, which were subjected to 24-hour periods of fasting. While fasting, researchers noted the mice exhibited a reduction in oxygen consumption (VO2), respiratory exchange ratio (RER), and energy expenditure, all of which were completely abolished by refeeding, which parallels results observed in humans.
"The reorganization of gene regulation by fasting could prime the genome to a more permissive state to anticipate upcoming food intake and thereby drive a new rhythmic cycle of gene expression. In other words, fasting is able to essentially reprogram a variety of cellular responses. Therefore, optimal fasting in a timed manner would be strategic to positively affect cellular functions and ultimately benefiting health and protecting against aging-associated diseases."
This study opens new avenues of investigation that could ultimately lead to the development of nutritional strategies to improve health in humans.
Sassone-Corsi first showed the circadian rhythm-metabolism link some 10 years ago, identifying the metabolic pathways through which circadian proteins sense energy levels in cells.
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Also contributing to the work were Kenichiro Kinouchi, Marlene Cervantes and Selma Masri from UCI's Department of Biological Chemistry, Center for Epigenetics and Metabolism; Christophe Magnan, Nicholas J. Ceglia, Yu Liu from UCI's Department of Computer Science, Institute for Genomics and Bioinformatics; Nunzia Pastore, Tuong Huynh and Andrea Ballabio from Baylor College of Medicine in Houston, Texas; and, Pierre Baldi of UCI's Institute for Genomics and Bioinformatics.
Kenichiro Kinouchi was supported by a Japan Society for the Promotion of Science(JSPS) fellowship. Christophe Magnan, Nicholas Ceglia, Yu Liu and Pierre Baldi were supported by grants from the Defense Advanced Research Projects Agency (DARPA; D17AP00002) and NIH (GM123558) to Pierre Baldi. This study was supported by the NIH, a Novo Nordisk Foundation Challenge Grant, and INSERM (France).
About the UCI School of Medicine
Each year, the UCI School of Medicine educates more than 400 medical students, as well as about 130 doctoral and master's students on the Irvine, California campus. More than 700 residents and fellows are trained at UC Irvine Medical Center in Orange, California and at other affiliated institutions. The highly regarded medical school is accredited by the Liaison Committee on Medical Accreditation and ranks among the U.S. News & World Report's top 50 medical schools in the nation for research. Dedicated to advancing medical knowledge and clinical practice through scholarly research, physician education, and high-quality care, the school of medicine offers MD, MS, and PhD Degrees; a Master of Science in Biomedical and Translational Science (MS-BATS), combined MD/MBA, MD/MS-BATS, and MD/MPH programs; and a distinctive combined MD/master's program called the Program in Medical Education for the Latino Community (PRIME-LC). For more information, visit: som.uci.edu.
About the University of California, Irvine
Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. Located in one of the world's safest and most economically vibrant communities, UCI is Orange County's second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.
Journal
Cell Reports