Estudies developed by researchers at Unicamp revealed that a hormone produced in the hypothalamus, called Melanin Concentrating Hormone (MCH), has the dual role of controlling energy expenditure and insulin production in the body. The work, which resulted in the recent publication of an article in the North American magazine Endocrinoloy, from the Endocrine Society, paves the way for therapeutic actions aimed at combating diabetes mellitus, which affects 9% of Brazilians and is normally associated with obesity. The connection between the two diseases arises from the fact that insulin, while acting on peripheral organs to control the amount of glucose in the blood, also acts on the brain to control hunger.

Disease is associated with obesity

“Complex connections participate in a cycle that controls hunger, energy expenditure, and the production and action of insulin in multiple organs”, explains professor at the Faculty of Medical Sciences (FCM) and head of the Cell Signaling Laboratory, Licio Velloso, who coordinates the research. “We found that MCH plays an important role in these connections and, therefore, becomes an interesting target for a common therapeutic approach for patients with diabetes and obesity”, he adds. The studies coordinated by Velloso included collaboration with other groups at Unicamp, led by professors Mário JA Saad, also from FCM, and Antonio Carlos Boschero and Everardo M. Carneiro, from the Institute of Biology. (IB).

The study developed at Unicamp focused on the expression of 1.176 genes in the hypothalamus of obese mice fed a high-fat diet. Of this total, 169 suffered changes as a result of food. By studying each of them separately, the researchers verified the dual function of MCH in controlling energy expenditure and insulin production in the body.

According to Velloso, drugs that control the production of MCH are being evaluated at Unicamp and in research centers in other countries. “There is a real worldwide race to find these medicines that, in the future, will possibly be used to treat these diseases”, says the doctor. At Unicamp, the tests consist of controlling the production of MCH in the animals' hypothalamus. Experiments show that obese individuals have more MCH, which causes them to use less energy. In lean individuals, there is less MCH and greater calorie burning. Animals that received extra doses of MCH also started to develop resistance to the action of insulin, becoming diabetic. “They produce more insulin but their functioning is inadequate,” he explains.

Insulin is a hormone produced exclusively by specialized cells in the pancreas, called beta cells. Its production occurs after food intake. For the glucose obtained through food to leave the blood and enter the cells of various tissues where it will participate in energy production, insulin must be present and function properly. In addition to promoting glucose uptake, insulin acts on the hypothalamus, producing the feeling of satiety. The hypothalamus is the region of the brain that controls autonomic functions such as hunger, sleep, thirst and thermogenesis (energy expenditure necessary to maintain vital functions).

When an individual develops the most common form of diabetes (type 2 diabetes), according to Velloso, it is observed that despite still having insulin, it no longer acts as effectively as before. “As a result, there is a failure to inhibit hunger and the person starts to eat more and gain weight”, he explains. “Resistance to insulin action in other regions of the body favors the development of diabetes, while insulin resistance in the brain favors the development of obesity”, he adds.

Another factor that associates diabetes with obesity is the finding that diets rich in fat interfere with the insulin receptor in the cell. To transform glucose into energy, insulin needs to bind to a receptor anchored in the cell membrane. In certain situations, this receptor does not work correctly, which causes diabetes. According to Velloso, one of the possible reasons for this is the high-fat diet.

“Our goal is to come up with a drug that acts on the hypothalamus to reduce the production of MCH, which will make it possible to increase energy expenditure and improve the action of insulin in peripheral organs,” says Veloso. According to him, although studies on animals began around four years ago, it is still too early to talk about tests on humans. “The production of a new medicine depends on very meticulous evaluation steps,” he explains. The clinical stage with human patients is divided into four phases and is only started after satisfactory results in animals.

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