Scientists Unlocked the Secret of Genetic Impact of Time-restricted Eating in Mice

Scientists from San Diego-based Salk Institute for Biological Studies have recently shown in mice how TRE influences gene expression across more than 22 regions of the body and brain. These findings, published in the January 3, 2023 issue of Cell Metabolism, have implications for a range of conditions, including diabetes, heart disease, hypertension, and cancers in which TRE has shown potential benefits.

Related Article: Scientists Identify New Genetic Variant Related to Obesity

Reshaping Gene Expression Throughout the Body

Time-restricted eating or feeding (TRE or TRF) is a nutrition intervention approach in which all daily calorie intake is restricted within a consistent daytime window of approximately 8 to 10 hours. The TRE approach has shown multiple health benefits in a number of studies, including improvements in sleep, blood pressure, cardiac function, and gut health, as well as reductions in cancer risk and tumor growth. In spite of these benefits, it has not been understood precisely how it affects the body on a molecular level or how those changes interact across multiple organ systems.

For the study, which lasted for 7 weeks, two groups of mice were fed the same high-calorie diet. The ad libitum feeding (ALF) group was given free access to the food, while the TRF group was restricted to eating within a feeding window of 9 hours each day. The team of researchers, led by Prof. Satchidananda Panda, aimed to assess diurnal changes to the transcriptome in tissues from mice subjected to ALF or TRF, respectively. 

After 7 weeks, tissue samples from both groups of mice 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.

Overall, researchers found that approximately 70% of mouse genes respond to time-restricted eating. In particular, about 40% of genes in major organs for hormonal regulations such as adrenal gland, hypothalamus and pancreas were affected by TRF. Given that 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 health issues.

Concerning the digestive tract, genes involved in upper parts of the small intestine (duodenum and jejunum) were activated by TRF while those in the lower part (ileum) remained relatively unaffected. It was also found that TRF aligned the circadian rhythms of multiple organs of the body. Researchers could take advantage of this finding to investigate the effects that shift work has on digestive diseases and cancers, since it disrupts the bodies’ circadian rhythm. 

Other notable findings related to the effects of TRF on gene expression include the decrease in genes involved in inflammatory signaling and glycerolipid metabolism, and the increase in genes involved in RNA processing, protein folding, and autophagy. In addition, TRF induces significant changes in gene expression involved in metabolism of branched-chain amino acids (BCAA), glucose, and lipids. According to Prof. Panda, changing the timing of food altered gene expression not only in the gut and liver, but also thousands of genes in the brain.

Opening up Vast Opportunities for Future Studies

One of the major limitations of this study is that the transcriptome data was generated only from young, male mice. Future studies will be needed to understand how TRF-dependent gene expression changes across tissues are affected by sex and age. 

In the future, Prof. Panda’s team will also examine how TRF impacts specific conditions or systems implicated in the study, including atherosclerosis, which is a hardening of the arteries that is a precursor to heart disease and stroke, as well as chronic kidney disease (CKD). Furthermore, clinical trials can be conducted to evaluate the efficacy of TRF in the prevention and management of chronic diseases.

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Author

Richard Chau