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Time-restricted feeding impacts gene expression in multiple organs

A recent study has revealed that time-restricted feeding significantly impacts gene expression in mice. The work, published this week in Cell Metabolism, describes the system-wide impacts that occur as a result of this intermittent fasting and the potential implications for human health.

What is time-restricted feeding?

Time-restricted feeding is a form of intermittent fasting that involves splitting a 24-hour period into fasting and non-fasting time frames. Typically, all food intake will occur during a period of around eight to ten hours. Restricting food consumption in this way is known to have nutritional benefits in humans and is linked to decreased risk of certain cancers and conditions such as high blood pressure. Despite vast research on the topic, the underlying reasons for this remain unknown – although transcriptome changes have been previously implicated.

In an attempt to uncover the mechanisms behind these health benefits, the team from the Salk Institute analysed gene expression in various organs in mice to compare outcomes between those subjected to time-restricted feeding and those fed over a more traditional, unrestricted 24-hour (ad libitum) period.

A high-calorie experiment

The two groups of mice were fed the same high-calorie diet during the study – the only difference being the time frame in which it was provided. The animals were exposed to a diurnal cycle of 12-hours each of light and darkness. After seven weeks, gene expression in multiple organs was examined every two hours over a 24-hour time period using RNA-sequencing. This allowed for an analysis of the animals’ circadian rhythms in response to their diet.

The mice who were not subject to time-restricted feeding suffered weight gain and metabolic dysfunction over the course of the study. These effects were not seen in the restricted group. Expression of over 80% of the genes studied were revealed to be altered in the time-restricted group in response to diet. Gene expression was affected not only in a quantitative manner, but also rhythmically, with the time-restricted group exhibiting two distinct, diurnal periods of differential gene expression.

The effects were seen system-wide, with most tissues subject to gene expression alterations in some form. The affected genes included many which are known to control hormone expression and other vital biological processes – implying wide reaching effects on the body beyond basic nutrition.

Figure 2: Image showing different biological pathways affected by time-restricted feeding. Each large circle represents a different pathway. Each smaller red or blue circle indicating a gene that was either up- or down-regulated in the time-restricted feeding (TRF) group.

You are(n’t) what you eat

It goes without saying that diet is one of the most important risk factors for human health. However, this study shows that, in mice, the impacts of diet reach beyond what you choose to eat – the timing also matters. The knock-on effects of a high-calorie diet, such as the one used here, can potentially be mitigated through careful timing of food intake.

The distinct stages of differential gene expression observed in mice as a result of the time-restricted diet showed that an organism’s inbuilt circadian rhythm is not the only significant trigger for phased gene expression. This finding is of particular interest, as disruption to the circadian rhythm has been previously linked to negative health outcomes in humans and other animals.

The observation that a time-restricted diet could impact gene expression in a similar rhythmic manner could be used to mitigate health risks in shift workers, for example. These individuals often need to eat, sleep and exercise at unconventional hours and are at a higher risk of health problems than traditional workers. The gene expression changes seen in this study could be linked to the onset of various conditions – researcher Satchidananda Panda stated that the “results open the door for looking more closely at how this nutritional intervention activates genes involved in specific diseases, such as cancer.”

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