Intermittent fasting improves well being with out altering the physique’s core clock


For the first time, scientists have investigated the early effects of temporary feeding on the daily periodic oscillations of metabolites and genes in muscle and metabolites in blood. Findings from scientists from the University of Copenhagen, the Australian Catholic University, and the Karolinska Institutet show that time-limited feeding has no impact on the core clock of the muscle and open the door for further investigation into how these observed changes improve health.

When it comes to metabolic health, it’s not just what you eat, but when you eat it. Studies have shown that one effective way to lose weight and fight obesity is to reduce the number of hours in the day that you eat. Temporary feeding – also known as intermittent fasting – has also been shown to improve health even before weight loss begins.

The biological explanation for the phenomenon is still little known. Scientists from the University of Copenhagen, the Australian Catholic University, and the Karolinska Institutet therefore examined the body’s early adaptations to temporary feeding. Their study identified a number of key changes in muscle genetic activity, as well as muscle fat and protein levels, that could explain the beneficial effects of time-limited feeding.

Intermittent fasting body clock

Principal Component Analysis (PCA) of samples based on skeletal muscle genes (a), skeletal muscle metabolites (b) and serum metabolites (c), where the color indicates the sampling time. The circle indicates the extended feeding (EXF) and the triangle indicates the limited time feeding (TRF). t-SNE clustering of periodic transcripts in skeletal muscle according to EXF (d) and TRF (e). Periodic metabolites in skeletal muscle according to EXF (f) and TRF (g) and serum metabolites according to EXF (h) and TRF (i). n = 11 participants. Photo credit: Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen

New findings on short-term, time-limited feeding

The study marks the first time that scientists have examined the oscillations of metabolites in skeletal muscle and blood, and gene expression in skeletal muscle after temporary feeding. By focusing on the short-term and early effects of limited-time feeding, the goal was to separate the signals that determine health from those associated with weight loss.

“We observe that the rhythm of the genes of the skeletal muscle core clock remains unchanged by time-limited feeding, which suggests that differences are more due to diet than to inherent rhythms,” says postdoc Leonidas Lundell of the Novo Nordisk Foundation Center for Basic Metabolic Research ( CBMR) at the University of Copenhagen.

“We also see that the metabolite profile of skeletal muscle changes from predominantly lipid-based to amino acid-based after time-limited feeding. This coincides with changes in the rhythmicity of amino acid transporters, suggesting that some of the amino acid profile could be due to absorption from the blood. “

Research Associate Evelyn Parr of the Mary MacKillop Institute for Health Research at the Australian Catholic University added, “Our research is an important step in understanding how limited-time eating improves metabolic health while bridging the gap between animal models and human intervention studies can close. It was important to capture these early metabolic responses before assessing what changes may occur after a long period of time following a time-limited feeding pattern. “

Eating behavior has no influence on the body’s core clock

In the study, 11 overweight / obese men were assigned one of two nutritional protocols, either unrestricted feeding or eight hours of timed feeding, for a period of five days. On the fifth day, samples were taken every four hours for a full day. After a 10-day break, they repeated the experiment on the different diet protocol.

After each procedure, the team of scientists examined gene expression in muscles and the profile of metabolites – molecules that are formed by metabolic processes – in blood and muscles.

They discovered that time-limited feeding changed the rhythmic concentration of metabolites in blood and muscles. Temporary feeding also influenced the rhythmic expression of genes expressed by the muscle, particularly those responsible for transporting genes

Amino acids are a series of organic compounds that are used to make proteins. There are approximately 500 naturally occurring amino acids known, although only 20 appear in the genetic code. Proteins are made up of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a biologically active form. The amino acid sequences of proteins are encoded in the genes. Nine proteinogenic amino acids are called “essential” for humans, since they cannot be produced by the human body from other compounds and must therefore be consumed as food.

“class =” glossaryLink “> amino acids, the building blocks of proteins.

Critically, the study showed that the temporary feeding does not change the core clock of the muscle – the built-in metronome of the cell that regulates the daily cycle of activity. This suggests that the changed rhythmicity of the metabolite and gene expression caused by temporary feeding may be responsible for the positive effects on health.

“Our results open up new possibilities for scientists who want to understand the causal relationship between temporary feeding and improved metabolic health. These findings could help develop new therapies to improve the lives of people with obesity, ”says Professor Juleen Zierath from the Karolinska Institutet and CBMR at the University of Copenhagen.

Reference: “Temporary feeding changes the rhythmicity of lipid and amino acid metabolites without disturbing the gene expression of the clock” by Leonidas S. Lundell, Evelyn B. Parr, Brooke L. Devlin, Lars R. Ingerslev, Ali Altıntaş, Shogo Sato, Paolo Sassone- Corsi, Romain Barrès, Juleen R. Zierath and John A. Hawley, September 16, 2020, Nature Communications.
DOI: 10.1038 / s41467-020-18412-w

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