Research Shows Intermittent Fasting Enhances Health Without Affecting the Body’s Core Clock

​In a first, researchers have studied the early impacts of time-restricted eating on the daily periodic fluctuations of metabolites and genes in muscle, and metabolites in blood.

The research made by scientists at the University of Copenhagen, the Australian Catholic University, and Karolinska Institutet finds that time-restricted feeding doesn’t affect the muscle’s core clock, and opens the possibility to more research on the way these observed changes enhance health.

The Biological Explanation of Time-Restricted Feeding is Not Understood

When talking about metabolic health, it is not just what you consume; it is also when you eat it. Numerous studies have demonstrated that one effective means of losing weight is to decrease the number of hours in the day that you eat. Time-restricted feeding, also known as intermittent fasting, has also been shown to enhance health even before weight loss starts to show up.

The biological explanation for this phenomenon is still mainly not understood. Therefore, scientists from the University of Copenhagen, the Australian Catholic University, and Karolinska Institutet analyzed the body’s early adaptations to time-restricted feeding.

The research found a number of key changes in the genetic activity of muscles, as well as the content of muscle fats and proteins, which could clarify the positive effect of intermittent feeding.

New Insights on Short-Term Intermittent Fasting

The study is the first time researchers have analyzed the fluctuations of metabolites in skeletal muscle and in blood, as well as gene expression in skeletal muscle after intermittent fasting. By observing the short-term and early impacts of time-restricting feeding, the aim was to unravel the signals that govern health from those linked to weight loss.

“We observe that the rhythm of skeletal muscle core clock genes is unchanged by time-restricted feeding, suggesting that any differences are driven more by diet, rather than inherent rhythms,” says Postdoc Leonidas Lundell, from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

The scientist added: “We also see that the metabolite profile of skeletal muscle switches from being predominantly lipid-based to amino acid-based, after time-restricted feeding. This coincides with changes in rhythmicity of amino acid transporters, indicating that part of the amino acid profile could be due to absorption from the blood.”

Principal component analysis (PCA) of samples based on skeletal muscle genes (a), skeletal muscle metabolites (b), and serum metabolites (c), with color indicating sampling time. Circle indicates extended feeding (EXF), and triangle indicates time-restricted feeding (TRF). t-SNE clustering of periodic transcripts in skeletal muscle after EXF (d), and TRF (e). Periodic metabolites in skeletal muscle after EXF (f), and TRF (g), and serum metabolites after EXF (h), and TRF (i). n = 11 participants. [Image Credit: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen]
Research Fellow Evelyn Parr from the Mary MacKillop Institute for Health Research at the Australian Catholic University, added: “Our research is an important step towards understanding how time-restricted eating can improve metabolic health while bridging the gap between animal models and human intervention studies. It was important to capture these early metabolic responses before assessing what changes might occur after a longer period following a time-restricted feeding pattern.”

Eating Behavior Does Not Affect the Body’s Core Clock

As part of the research, 11 men with overweight or obesity were given one of two eating systems for a total of five days – either unrestricted diet or eight-hours of time-restricted feeding. On the fifth day, samples were taken every four hours for the whole day, and after a 10-day break, they repeated the experiment with the other eating protocol.

After each assignment, the team of researchers analyzed the gene expression in muscles, as well as the profile of metabolites – molecules that form through metabolic processes – in the blood and muscles as well.

They found that intermittent fasting​ changed the rhythmic concentration of metabolites in blood and muscle. Time-restricted feeding also affected the rhythmic expression of genes expressed by muscle, more so those liable for aiding the transport of amino acids, the building blocks of proteins.

Crucially, the research showed that intermittent fasting​ did not alter the muscle’s core clock, which is the cell’s default metronome that regulates its daily cycle of activity. This implies that the changed rhythmicity of metabolite and gene expression produced by time-restricted feeding could be the cause behind the positive health impact.

“Our findings open new avenues for scientists who are interested in understanding the causal relationship between time-restricted feeding and improved metabolic health. These insights could help develop new therapies to improve the lives of people who live with obesity,” says Professor Juleen Zierath from Karolinska Institutet and CBMR at the University of Copenhagen.

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