Nav: Home

In mice, feeding time influences the liver's biological clock

April 16, 2019

The timing of food intake is a major factor driving the rhythmic expression of most genes in the mouse liver, researchers report April 16th in the journal Cell Reports. The findings demonstrate that body-wide signals driven by rhythmic food intake significantly contribute to driving rhythms in liver metabolic functions and gene expression independently of the liver and clock.

"In contrast to the prevailing model in the field currently, our findings indicate that feeding times do more than just synchronize the molecular clock in different organs--they actually can regulate rhythmic gene expression in parallel of the clock," says senior study author Jerome Menet (@jsmenet), whose lab at Texas A&M University studies the mammalian circadian clock. "This raises the interesting hypothesis that eating at the wrong time of the day, which is prevalent in shift-workers for example, can desynchronize rhythmic gene expression and lead to pathologies."

Nearly every mammalian cell harbors a molecular circadian clock that drives rhythmic gene expression to coordinate daily cycles in metabolism, physiology, and behavior. These clocks are synchronized by the master circadian pacemaker located in a brain structure called the suprachiasmatic nucleus (SCN). The SCN uses multiple cues, such as rhythms in neuronal signaling, hormone secretion, body temperature, and food intake, to synchronize outlying clocks located in various organs throughout the body, ensuring that they are all properly entrained to the environment.

Entrained peripheral clocks are thought to then regulate rhythmic gene expression in a cell-autonomous manner, that is, independently within each cell, to start tissue-specific circadian transcriptional programs that control the rhythmicity of biological processes. In contrast to current models, the new findings show that rhythmic food intake largely drives rhythmic gene expression independently of the cell-autonomous molecular clock in the liver.

To examine the role of rhythmic food intake in circadian biology and rhythmic gene expression, Menet and his team fed mice arrhythmically, at night only, or in an unrestricted manner for five weeks, then collected the livers of the mice at different times of day and examined the expression of liver genes.

Compared to unrestricted feeding, arrhythmic feeding disrupted oscillations in the expression of 70% of cycling liver genes without affecting the core molecular clock in the liver. Moreover, the timing of food intake regulated many metabolic pathways in the liver, including those involved in cholesterol and glycogen synthesis. Taken together, the findings suggest that the master circadian clock in the SCN does not act solely to synchronize peripheral circadian clocks but instead contributes more generally to circadian transcriptional programs throughout the body.

In future studies, Menet and his team will examine whether the timing of food intake regulates rhythmic protein production, as well as rhythmic gene expression in various tissues. Another question for future research is whether other SCN-driven cues such as body temperature drive rhythmic gene expression in peripheral clocks.

For now, the health implications of the new findings remain unclear. Clock disruptions have been associated with aging, altered responses to therapeutics, obesity, diabetes, mental health disorders, and cancer. According to the study authors, these effects could potentially be ameliorated by controlling the timing of food intake. "But one should not assume that because we observe a strong effect of rhythmic food intake in the liver of mouse, this also applies to other mouse tissues, and even to the human liver," Menet says.
-end-
This work has been supported by startup funds from Texas A&M University.

Cell Reports, Greenwell et al.: "Rhythmic Food Intake Drives Rhythmic Gene Expression More Potently than the Hepatic Circadian Clock in Mice" https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30394-8

Cell Reports (@CellReports), published by Cell Press, is a weekly open-access journal that publishes high-quality papers across the entire life sciences spectrum. The journal features reports, articles, and resources that provide new biological insights, are thought-provoking, and/or are examples of cutting-edge research. Visit: http://www.cell.com/cell-reports. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Body Temperature Articles:

Whole body ownership is not just the sum of each part of the body
Differences between whole body and body part ownership were clarified using scrambled body stimulation in a virtual environment, wherein the observer's hands and feet were presented in randomized spatial arrangements.
How diarrhea pathogens switch into attack mode at body temperature
Many bacterial pathogens excrete toxins as soon as they have entered the host in order to suppress its immune response.
Human body temperature has decreased in the United States, Stanford study finds
Since the early 19th century, the average human body temperature in the United States has dropped, according to a study by researchers at the Stanford University School of Medicine.
T-shirt generates electricity from temperature difference between body and surroundings
Researchers of the Faculty of Science of the University of Malaga (UMA) have designed a low-cost T-shirt that generates electricity from the temperature difference between the human body and the surroundings.
Thermal siphon effect: heat flows from low temperature to high temperature
In this work, researchers study (both thermal and electric) energy transport in physical networks that rewired from 2D regular lattices.
Short-term study suggests vegan diet can boost gut microbes related to body weight, body composition and blood sugar control
New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (Sept.
Gut microbiota helps to maintain core body temperature under cold exposure
A research group led by Professor John R. Speakman from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, has revealed the important role of gut microbiota in thermoregulation -- the way animals respond to cold exposure.
High-temperature electronics? That's hot
A new organic polymer blend allows plastic electronics to function in high temperatures without sacrificing performance.
Cryo-EM reveals structure of protein responsible for regulating body temperature
A team led by Van Andel Research Institute (VARI) scientists has revealed for the first time the atomic-level structure of TRPM2, a protein that may be a promising drug target for conditions such as Alzheimer's disease and bipolar disorder.
Body temperature regulation: how fever comes
Researchers from Kanazawa University report in Journal of Neuroscience performed a microdialysis study on mice to determine mechanisms underlying the inflammatory response in the brain associated with fever that might be used to develop new strategies for treatment.
More Body Temperature News and Body Temperature Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.