At the tail end of the holiday season, many of us have grown accustomed to ad libitum feeding—eating without restriction. Moreover, some of our New Year’s resolutions may focus on counteracting just that, with the hope of losing weight. Indeed, studies have shown that time-restricted eating may offer health benefits and increase life span. However, exactly how time-restricted eating affects the body on the molecular level, and how those changes interact across multiple organ systems, has not been well established. Now, a new study shows, in mice, how time-restricted eating influences gene expression across more than 22 regions of the body and brain. The research has implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

The findings are published in Cell Metabolism in the article, “Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals.”

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” said Satchidananda Panda, PhD, professor of the Regulatory Biology Laboratory at Salk. “Our results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group was given free access to food. The other group was restricted to eating within a feeding window of nine hours 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. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

The authors found that 70% of mouse genes responded to time-restricted eating.

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

Nearly 40% of genes in organs important for hormonal regulation—such as the adrenal gland, hypothalamus, and pancreas—were affected by time-restricted eating. Because hormonal imbalance is implicated in many diseases from diabetes to stress disorders, these results offer guidance to how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine (the duodenum and jejunum) were activated by time-restricted eating, the ileum was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupt circadian rhythms, impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shift workers.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs of the body. “Circadian rhythms are everywhere in every cell,” said Panda. “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.”

Next, the researchers plan to take a closer look at the effects of time-restricted eating on specific conditions or systems implicated in the study, such as atherosclerosis, which is a hardening of the arteries that is often a precursor to heart disease and stroke, as well as chronic kidney disease.

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