Their experiments in mice revealed that the daily waxing and waning of thousands of genes in the liver—the body’s metabolic clearinghouse—is mostly controlled by food intake and not by the body’s circadian clock as conventional wisdom had it.
“If feeding time determines the activity of a large number of genes completely independent of the circadian clock, when you eat and fast each day will have a huge impact on your metabolism,” says the study’s leader Satchidananda (Satchin) Panda, Ph.D., an assistant professor in the Regulatory Biology Laboratory.
The Salk researchers’ findings, which will be published in a forthcoming issue of the Proceedings of the National Academy of Sciences, could explain why shift workers are unusually prone to metabolic syndrome, diabetes, high cholesterol levels and obesity.
“We believe that it is not shift work per se that wreaks havoc with the body’s metabolism but changing shifts and weekends, when workers switch back to a regular day-night cycle,” says Panda.
In mammals, the circadian timing system is composed of a central circadian clock in the brain and subsidiary oscillators in most peripheral tissues. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior. The clocks in peripheral organs are largely insensitive to changes in the light regime. Instead, their phase and amplitude are affected by many factors including feeding time.
The clocks themselves keep time through the fall and rise of gene activity on a roughly 24-hour schedule that anticipates environmental changes and adapts many of the body’s physiological function to the appropriate time of day.
“The liver oscillator in particular helps the organism to adapt to a daily pattern of food availability by temporally tuning the activity of thousands of genes regulating metabolism and physiology,” says Panda. “This regulation is very important, since the absence of a robust circadian clock predisposes the organism to various metabolic dysfunctions and diseases.”
Despite its importance, it wasn’t clear whether the circadian rhythms in hepatic transcription were solely controlled by the liver clock in anticipation of food or responded to actual food intake.
To investigate how much influence rhythmic food intake exerts over the hepatic circadian oscillator, graduate student and first author Christopher Vollmers put normal and clock-deficient mice on strictly controlled feeding and fasting schedules while monitoring gene expression across the whole genome.
He found that putting mice on a strict 8-hour feeding/16-hour fasting schedule restored the circadian transcription pattern of most metabolic genes in the liver of mice without a circadian clock. Conversely, during prolonged fasting, only a small subset of genes continued to be transcribed in a circadian pattern even with a functional circadian clock present.
“Food-induced transcription functions like a metabolic sand timer that runs for 24 hours and is continually reset by the feeding schedule while the central circadian clock is driven by self-sustaining rhythms that help us anticipate food, based on our usual eating schedule,” says Vollmers. “But in the real world we don’t eat at the same time every day and it makes perfect sense to increase the activity of metabolic genes when you need them the most.”
For example, genes that encode enzymes needed to break down sugars rise immediately after a meal, while the activity of genes encoding enzymes needed to break down fat is highest when we fast. Consequently a clearly defined daily feeding schedule puts the enzymes of metabolism in shift work and optimizes burning of sugar and fat.
“Our study represents a seminal shift in how we think about circadian cycles,” says Panda. “The circadian clock is no longer the sole driver of rhythms in gene function, instead the phase and amplitude of rhythmic gene function in the liver is determined by feeding and fasting periods—the more defined they are, the more robust the oscillations become.”
While the importance of robust metabolic rhythms for our health has been demonstrated by shift workers’ increased risk of developing metabolic syndrome, the underlying molecular reasons are still unclear. Panda speculates that the oscillations serve one big purpose: to separate incompatible processes, such as the generation of DNA-damaging reactive oxygen species and DNA replication.
Panda, for one, has stopped eating between 8 pm and 8 am and says he feels great. “I even lost weight, although I eat whatever I want during the day,” he says.
Researchers who also contributed the work include postdoctoral researcher Luciano DiTacchio, Ph.D., graduate students Sandhyarani Pulivarthy and Shubhrox Gill, as well as research assistant Hiep Le, all in the Regulatory Biology Laboratory.
The work was funded in part by the National Institutes of Health and the Pew Scholars Program in Biomedical Sciences.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes, and cardiovascular disorders by studying neuroscience, genetics, cell and plant biology, and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.
Gina Kirchweger | Newswise Science News
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research