Intermittent fasting has become a hot topic in the wellness industry, as numerous laboratory studies have shown the health benefits of time-restricted eating, including increased life expectancy.
However, exactly how it affects the body at the molecular level and how those changes interact across multiple organ systems has not been well understood. Now, Salk scientists show in mice how time-restricted feeding influences gene expression in more than 22 regions of the body and brain. Gene expression is the process by which genes are activated and respond to their environment by creating proteins.
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The findings, published in Cell Metabolism on January 3, 2023, have implications for a wide range of health conditions where 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,” says Professor Satchidananda Panda, lead author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door to take a closer look at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”
For the study, two groups of mice were given the same high-calorie diet. One group was given free access to food. The other group was restricted to eating within a nine-hour feeding window each day.
After seven weeks, tissue samples from 22 groups of organs and the brain were collected 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 percent of mouse genes respond to time-restricted feeding.
“By changing the timing of the meal, we were able to change gene expression not just in the gut or liver, but also in thousands of genes in the brain,” says Panda.
Nearly 40 percent of genes in the adrenal gland, hypothalamus, and pancreas were affected by time-restricted feeding. These organs are important for hormonal regulation. Hormones coordinate functions in different parts of the body and the brain, and hormonal imbalance is implicated in many diseases, from diabetes to stress disorders. The results offer guidance on how time-restricted feeding can help control these diseases.
Interestingly, not all sections of the digestive tract were affected equally. While the genes involved in the two upper portions of the small intestine, the duodenum and the jejunum, were activated by time-restricted feeding, the ileum, at the lower end of the small intestine, was not.
This finding could open up a new line of research to study how shift work, which disrupts our 24-hour biological clock (called the circadian rhythm), affects digestive diseases and cancer. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who typically work in shifts.
The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs in the body.
“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized circadian rhythms to have two main waves: one during fasting and one just after eating. We suspect this allows the body to coordinate different processes.”
Next, Panda’s team will 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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