Weizmann Institute of Science scientists tested the control of the biological clock on metabolic processes in the mitochondria. The results of their research may, in the future, help in the development of obesity and slimming diets that will be based on the hours of eating, and not on the amount of food a person eats, thus helping both the populations suffering from a lack of food, and those suffering from an excess consumption of food.
The scientists, led by Dr. Gad Asher From the department of biomolecular sciences at the institute, the interrelationships between these clocks ("circadian clocks") and metabolic processes in our bodies are being studied. Results of research carried out by Dr. Adi Neufeld-Cohen, from Dr. Asher's group, in collaboration with Dr. Maria Robles and Prof. Matthias Mann from the Max Planck Institute for Biochemistry in Germany, were published recently In the scientific journal "Records of the American Academy of Sciences" (PNAS).
"The environment on Earth, where there is a 24-hour day, caused, through evolution, the development of biological clocks," says Dr. Asher. "These clocks, found in bacteria, flies, humans and more, measure time even without external stimulation. They play a central role in controlling the rhythms of sleep, activity, eating, metabolism, in a 24-hour cycle. In a certain sense, this is a kind of diary that tells our body what is expected, so that the body can prepare for what is to come and act optimally."
The biological clocks control most of the metabolic processes in the body. Almost everyone has a 24-hour cycle: this is the case at the physiological level in the entire organism (blood pressure, sugar levels, and hormone levels), and so is at the molecular level (enzymes and metabolic pathways that have one peak per day). Because of this, the disruption of the biological clock causes damage to several biological processes. Thus, for example, mice that have genetic damage to their biological clock, as well as people who work shifts that disrupt their circadian clock, suffer from obesity, diabetes, and metabolic syndrome.
The scientists examined the control mechanisms through which the biological clock affects the metabolism in the cell, and its energy output and consumption. The "energy station" of the cell operates in a tiny intracellular organelle, called a mitochondrion (in plural, mitochondrion). The scientists checked whether during the day certain proteins that are essential for its function accumulate in the mitochondria, in circulation, and affect its energy output. They discovered that about 40% of the mitochondrial proteins, among the hundreds of proteins that were identified and quantified, accumulate in a circadian manner; That is, during a day there is one peak in their quantity, and this process is mostly controlled by the circadian clock. Surprisingly, most of the circadian proteins in the mitochondria accumulated within four hours after the start of the daily light cycle (the experiment was performed in mice that are active at night and sleep during the day).
Many of these circadian proteins are actually essential enzymes that determine the activity rate of the mitochondria. For example, a central enzyme that determines the rate of use of sugars for energy production accumulates at 4:00, so it is likely that at this time the ability to utilize sugars in the mitochondria will be at its peak. Therefore, the scientists provided the mitochondria with sugar, and found that indeed, around 4:00 o'clock the process of respiration and the utilization of sugar for energy production was at its peak, compared to its level during the rest of the day. In contrast, the protein responsible for the rate of entry of fatty acids into the mitochondria accumulated at 18:00, and the fatty acid utilization test showed that at that time fat processing was indeed optimal. In mice with a genetic mutation that damages their biological clock, there was no difference between the amount of these proteins during the day, and accordingly, the activity of breaking down the fats and sugars was constant throughout the day.
These findings strengthen the concept that the biological clock controls the changes in the rate of production and breakdown of certain substances in the body, and that it controls processes in the mitochondria both through a direct effect on it, and through an indirect effect on the substances that reach it, for example, through an effect on the organism's eating hours.
These findings may help us learn how to control the efficiency of utilizing certain nutrients, both when there is a shortage of it and when there is an excess of it. "In the past, we showed that if mice eat only at night, during their activity hours, and not when they want, they will eat the same amount of calories, but the levels of fat in their liver will be 50% lower," says Dr. Asher. "In other words, the result depends not only on what is eaten, but also on the time of eating. If we know how to correctly plan the right times for the body's activity, we may be able to utilize the various nutrients in a correct and healthier way."
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And what about humans?