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The secret to fighting obesity could lie in one area of our brain, making it easier to fight than we think.
This conclusion was reached by the distinguished Greek professor Konstantinos Stratakis, head of the Department of Genetics and Endocrinology at the National Institute of Child Health and Human Development (NICHD), which is part of the US National Institutes of Health (NIH). The study by Dr. Strataki’s science team was recently published in the prestigious scientific journal JCI Insight.
The study is already at the center of global scientific interest, as the new discovery could in the future offer doctors new tools to combat obesity, a phenomenon that is assuming epidemic proportions, mainly due to the modern way of life. For example, perhaps a simple nasal spray could encourage patients not only to exercise, but also to avoid unhealthy foods.
Dr. Strataki’s team found that by inactivating a gene in the brain of mice (Prkar2a) there is a decreased willingness to eat delicious food and a greater motivation for voluntary exercise. The study certainly emphasizes that “exercise and a healthy diet remain the first line of treatment for obese patients.”
Dr. Stratakis and his team decided to test Prkar2a, as it is a gene that encodes the regulatory subunit 2a of cAMP-dependent protein kinase (PKA) and is expressed basically only in reu, an area believed to be associated with the metabolic dysfunction.
“This area is associated with the reward ‘path’, with opposing stimuli, and with the processing of both positive and negative experiences. That is why it has been studied for nicotine addiction, frustration, depression, anxiety, and a host of other mood disorders, ”says Edra London, PhD, who works with Dr. Strataki and is the Lead author of the publication in the scientific journal JCI Insight.
Dr. Stratakis had already studied various PKA phenotypes in mice, as they are linked to cancer. “It’s an amazing phenotype, because to my knowledge, there is no other mouse, no other animal model that has this highly desirable phenotype where they want to exercise and avoid the reward of dessert,” says Dr. Stratakis.
However, when Dr. London began working in Dr. Strataki’s laboratory, he observed that Prkar2a-deficient mice were not as obese as wild-type mice. “My main interest was obesity, metabolic dysfunction. I’ve always been interested in understanding the overlap between obesity and addiction.” So this mouse was kind of a gift in a way, “says Dr. London.
In a previous study, Dr. Strataki’s team studied different PKA mouse models on high-fat diets. As they observed, after years of a high-fat diet, almost all the mice would eventually become obese. Some would stay a few minutes longer than others, but only for a limited time and would eventually become obese.
However, the researchers found that Prkar2a-deficient mice were better able to regulate calorie intake. Given the choice, the Prkar2a-deficient mice preferred the high-fat diet to the dry, low-fat diet, but could control the amount of food. “When we really measured accurately, we found that they actually ate less,” says Dr. London.
This finding prompted the team to continue with the initial investigation. So in the present study, they gave the mice free access to the wheels and found that although there are some mouse models in which the animals become hyperactive at night, this did not happen in this case. The mice seemed happy to run. They may have received some kind of neurochemical reward for this, the authors speculate.
“This is not yet clear, but it is a very interesting phenomenon and we are continuing to investigate it alongside the suppressed intake of fatty and delicious foods and also sugar,” says Dr London.
The fact that the mice seemed to enjoy running so much calmed the researchers who were concerned about lethargy, as these mice were not eating as much, which could be a sign of anxiety or depression. Dr. Strataki’s team tells Endocrine News that she and her colleagues performed basic behavioral tests to look for stress, to see if the mice eventually tried to avoid certain situations, but found no signs of stress.
In fact, the only negative attitude the mice showed was when they were denied access to their wheels. At one point, the researchers put invisible locks on the wheels so the mice could enter the wheels, but without turning. “It was very interesting to see the parts of the brain that were stimulated by this immediate premature gene expression,” says Dr. London. Dr. Stratakis explains that they used a brain pointer to monitor which parts were stimulated when the mice did not have a chance to run (parts of the brain that show anger).
Discovering the secrets of the brain
Dr. Stratakis and Dr. London point out that this research may not be an explanation for all types of obesity. However, since the Prkar2a gene is expressed in an area of the brain associated with addiction, they estimate that by targeting this gene they will be able to receive some responses to eating disorders.
“Again, this is an area of the brain that hasn’t been fully explored, but it might give us insight into cravings and the overlap between addiction and obesity, in the same way that some people are susceptible to substance abuse when others are not. is. “It’s nice to see that PKA clearly plays a role in different cell types and can control these two really basic behaviors in different directions.” London.
This research is still relatively new, and Dr. Stratakis, Dr. London, and their team continue to search for mechanistic explanations for this phenotype and phenomenon. Dr. London says that he will now look at the effects of a high-fat diet on the function of various genes involved in dopamine, serotonin, and other neurotransmitters. “We tried to explore in a different way, looking at possible small molecule inhibitors, which I suppose goes hand in hand with dreaming of a nasal spray one day,” he says.
For his part, Dr. Stratakis points out that “the idea is that if someone finds a short-acting inhibitor that would act directly in the brain, for example, a nasal spray, if they woke up in the morning and wanted to exercise but not he was in the mood for exercise, he can take the nasal spray. his mood changed dramatically and he wanted to run. “
Currently, Dr. Stratakis hopes that other scientists will follow this research. He notes that the AMP circular signaling pathway has been extensively studied. As a result, it has received more Nobel Prizes in medicine and physiology than any other hormonal signaling pathway. “It is very important for endocrinology … it is impressive that in such a small part of the brain a very specific part of this important signaling pathway functions. And deactivating it leads to such a powerful phenotype.” AMP-circular labeling has been used widely as a pharmaceutical target for a variety of therapeutic applications, “says Dr. Stratakis.
“I think the differences that we see are beginning to highlight some of the underlying differences in our behavior and in how we react to stimuli.” The potential of this research is enormous, as it appears to be related to diet-induced obesity and other possible behaviors associated with the use and activities of harmful substances, “says Dr. London.
With information from ΑΠΕ-ΜΠΕ
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