Time-restricted feeding reshapes gene expression throughout the body

Timing calorie intake synchronizes circadian rhythms across multiple systems in mice.


Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention involving a daily feeding cycle and fasting. It has pleiotropic health benefits that arise from multiple organ systems, yet the molecular basis of TRF-mediated benefits needs to be better understood.

Now, Salk scientists use mice to demonstrate how time-restricted eating affects gene expression in more than 22 parts of the body and brain. Genes respond to their environment by producing proteins through gene expression.

Professor Satchidananda Panda, senior author, and holder of the Rita and Richard Atkinson Chair at Salk, said, “We found that there is a system-wide, molecular impact of time-restricted eating in mice. Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

Two groups of mice were fed an identical high-calorie diet for the study. One group was given free access to food, whereas the other group was restricted to eating just during a nine-hour feeding window each day. After seven weeks, tissue samples were taken at various times of the day and night from 22 organ groups and the brain, and they were then examined for genetic alterations. The tissues used in the samples came from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, kidney and intestine components, and various brain regions.

70% of mouse genes were found to respond to Time-restricted feeding. Time-restricted eating impacted about 40% of the pancreas, hypothalamus, and adrenal gland genes. The regulation of hormones relies on these organs. 

Hormonal imbalance is linked to various diseases, including diabetes and stress problems. Hormones coordinate functions in different sections of the body and brain. The findings provide recommendations on how time-restricted eating may assist in managing certain disorders.

Fascinatingly, not all parts of the digestive system were equally impacted. Time-restricted eating activated the genes in the duodenum and jejunum, the upper two sections of the small intestine, but not in the ileum, located at the lower end of the small intestine. 

This discovery may pave the way for new research into the effects of professions involving shift work, which mess with our circadian rhythm, our 24-hour biological clock. Panda’s team’s earlier studies revealed that time-restricted eating enhanced the health of firefighters, who frequently work shifts.

Panda said“Circadian rhythms are everywhere in every cell. We found that time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting and another just after eating. We suspect this allows the body to coordinate different processes.”

Scientists are further planning to study the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, a hardening of the arteries that is often a precursor to heart disease and stroke as chronic kidney disease.

Journal Reference:

  1. Shaunak Deota, Terry Lin, et al. Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals. Cell Metabolism. DOI: 10.1016/j.cmet.2022.12.006
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