Imbalance between brain and liver internal clocks leads to weight gain
When the liver’s internal clock becomes out of sync with the brain’s central clock, we tend to eat more frequently and in larger quantities, increasing the risk of obesity and type 2 diabetes. But if the connection between the liver and the brain is blocked, overeating stops. and healthy eating habits are restored. This is evidenced by research from the University of Pennsylvania (USA), which opens up new prospects in the prevention and treatment of diabetes and obesity.
The human body’s central clock, located in the suprachiasmatic nucleus of the hypothalamus, at the base of the brain, responds to the light-dark cycle of the 24-hour day. But all organs of the body have their own internal clock, which must be synchronized with the central clock, but which allows them to regulate activities whose cycles last less than 24 hours (for example, eating) or more (for example, ovulation). In the case of the liver, which is part of the digestive system, its clock is regulated by the cycles of eating and fasting.
“When the liver clock is not working correctly, it sends a signal to the brain: “Help!” Eating abnormal! “Do something!” he explains in an email. Vanguard Mitchell Lazar, director of the investigation. The brain, in an attempt to help, spoils everything even more. It responds by eating more and at any time, including times of day when it should be sleeping, researchers found in experiments on mice. “We were quite surprised by this change in behavior,” admits Lazar.
“It’s best not to eat at night because it sets the liver clock at the wrong time.”
Mitchell LazarResearch Director
Researchers have shown that both high-fat diets and obesity disrupt the liver’s internal clock, causing animals to eat more and more irregularly. This creates a vicious circle in which poor nutrition disrupts the brain’s central clock, which in turn causes poor nutrition.
But if the connection between the liver and brain is blocked, the vicious cycle is broken and animals stop gaining weight, even if they are fed a high-fat diet. “They tended to eat less, produce more heat, consume more oxygen, and be more active,” all factors that are associated with better metabolic health, the researchers report in the journal. Sciencewhere they present their results today.
“This is an outstanding study of circadian rhythms, one of the best in recent years; clearly shows how important the coordination of the circadian clocks of different organs is for our health,” emphasizes Salvador Aznar-Benitah, Icrea researcher at the Institute of Biomedical Research (IRB Barcelona), who notes that Mitchell Lazar is a world leader in this field. field. .
If the connection between the liver and brain is blocked, the behavior of eating too much food at the wrong time is suppressed.
To disrupt the connection between the liver and brain, the researchers cut the hepatic branch of the vagus nerve, a kind of two-way highway connecting the liver and brain. They studied the effects of cutting off communication only in the upstream direction, without affecting signals from the brain to the liver, which showed that the cause of the problem lies in the liver’s internal clock.
“The identification of this pathway opens up the possibility of reversing the obesity epidemic (with) new dietary, surgical and pharmacological strategies,” says Spanish biologist Noelia Martinez-Sánchez from the Oxford Center for Diabetes, Endocrinology and Metabolism (UK) in her analysis. article published in Science and co-written with David Ray. “The hepatic branch of the hepatic nerve is under development for new treatments.”
Cutting this branch of the vagus nerve in humans “may have side effects and would be a risky intervention; “We are not ready to try this strategy at this time,” Mitchell Lazar said. Vanguard. “It would be preferable to interrupt the hepatic branch noninvasively, such as with a drug” or with neuromodulation. The leader of the study proposes to study which molecules are involved in the transmission of signals from the liver to the vagus nerve, which will allow us to look for drugs to inhibit them.
Intermittent dieting can be beneficial, but the best way to do it may vary from person to person.
Pending the development of new treatments, research findings suggest that the tendency toward weight gain and diabetes can be prevented by preventing the liver’s internal clock from becoming unbalanced. “The liver clock responds to food intake, so timing of meals is critical. So it’s best not to eat at night because it resets the liver clock at the wrong time,” says Lazar.
Intermittent dieting can be beneficial, the researcher adds, but “there is disagreement about which intermittent dieting regimen is best, and it may be different for different people.” A recent study led by Salvador Aznar-Benita of IRB Barcelona showed that maintaining a structured eating schedule with long periods of fasting between meals regulates the circadian rhythm of muscle cells.
According to Aznar-Benita, “What is very important is that Lazar showed that if the liver clock is not coordinated with the brain clock, animals stop eating at the time they should eat, and this leads to metabolic pathologies. “One of the things that happens with age is that coordination between different organ clocks is lost, so this study points to possible therapeutic avenues for preventing this problem associated with aging.”