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Timing of caloric intake synchronizes circadian rhythms in multiple systems

Timing of caloric intake synchronizes circadian rhythms in multiple systems

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Summary: Time-restricted feeding affects gene expression in more than 22 areas in the brain and body. The findings have implications for a number of health disorders where time-restricted eating appears to have potential benefits.

source: Salk Institute

Numerous studies have shown health benefits of time-restricted eating, including increased lifespan in lab studies, making practices like intermittent fasting a hot topic in the wellness industry.

However, exactly how it affects the body at the molecular level and how these changes interact across multiple organ systems is not well understood.

Salk scientists are now showing in mice how time-restricted feeding affects gene expression in more than 22 areas of the body and brain. Gene expression is the process by which genes are activated and respond to the environment by making proteins.

The findings, published in Cellular metabolism on January 3, 2023 have implications for a wide range of health conditions for which time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension and cancer.

“We found that there is a system-wide molecular impact of time-restricted feeding in mice,” said Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk.

“Our results open the door to a closer look at how this dietary intervention activates genes involved in specific diseases, such as cancer.”

For the purpose of the study, two groups of mice were fed the same high-calorie diet. One group was given free access to the food. The other group was restricted to eating within a nine-hour eating window each day.

After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. The samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, various parts of the kidney and intestine, and various areas of the brain.

The authors found that 70% of mouse genes respond to time-restricted feeding.

“By changing the timing of feeding, we were able to change gene expression not only in the gut or in the liver, but also in thousands of genes in the brain,” says Panda.

Nearly 40% of the genes in the adrenal gland, hypothalamus and pancreas were affected by the time-restricted diet. These organs are important for hormonal regulation. Hormones coordinate functions in various parts of the body and brain, and hormonal imbalances are implicated in many diseases from diabetes to stress disorders. The results offer guidance on how time-restricted eating can help manage these diseases.

Interestingly, not all parts of the digestive tract are affected equally. While genes involved in the upper two parts of the small intestine — the duodenum and jejunum — were activated by time-restricted feeding, the ileum, at the lower end of the small intestine, was not.

The authors found that 70% of mouse genes respond to time-restricted feeding. Image is in the public domain

This finding could open a new line of research to investigate how shift work, which disrupts our 24-hour biological clock (called the circadian rhythm), affects digestive diseases and cancers. Previous research by Panda’s team has shown that time-restricted eating improves the health of firefighters who typically work shifts.

The researchers also found that time-restricted eating aligns the circadian rhythms of multiple organs in the body.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted feeding synchronizes circadian rhythms to have two large waves: one during fasting and another immediately after a meal. We suspect that this allows the body to coordinate various processes.

The Panda team will then look more closely at the effects of time-restricted eating on specific conditions or systems involved in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, because as well as chronic kidney disease.

See also

Timing of caloric intake synchronizes circadian rhythms in multiple systems

About this diet and genetic research news

Author: Press office
source: Salk Institute
Contact: Press Office – Salk Institute
Image: Image is in the public domain

Original research: Free access.
A daily transcriptome landscape of a multi-tissue response to time-restricted feeding in mammalsby Shaunak Deota et al. Cellular metabolism


Summary

A daily transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals

Accents

  • 80% of genes were differentially expressed or rhythmic in TRF in at least one tissue
  • TRF downregulates genes involved in inflammatory signaling and glycerolipid metabolism
  • TRF increases genes involved in RNA processing, protein folding, and autophagy
  • TRF causes a multi-tissue rearrangement of BCAA, glucose and lipid metabolism

Summary

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of eating and fasting. In both animals and humans, TRF has pleiotropic health benefits that emanate from multiple organ systems, but the molecular basis of TRF-mediated benefits is not well understood.

Here, we subjected mice to an isocaloric at will feeding (ALF) or TRF on a Western diet and examined gene expression changes in samples taken from 22 organs and brain regions collected every 2 hours over a 24-hour period.

We found that TRF profoundly affects gene expression. Nearly 80% of all genes show differential expression or rhythmicity in TRF in at least one tissue. Functional annotation of these changes reveals tissue- and pathway-specific effects of TRF.

These findings and resources provide a critical basis for future mechanistic studies and will help guide time-restricted feeding (TRE) interventions to treat various disease states with or without pharmacotherapies.


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