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Difficulty losing weight may have help growth hormone

Publicado em 27 fevereiro 2019

A group of researchers at the University of São Paulo (USP) found that growth hormone (GH), linked to bone development and growth in height, also works directly in the brain to save energy when weight loss.

The findings are published in the journal Nature Communications. "We found that the hormone known for decades was nothing more than imagined," said José Donato Junior, a professor at the Institute of Biomedical Sciences (ICB) at USP and one of the study authors.

"GH receptors are found in large amounts in the muscles, liver, tissues and organs that are directly involved in metabolic growth, but we have found that the brain is also filled with GH receptors," said Donato.

"Furthermore, we found that GH in the brain is not only involved in metabolic growth, but primarily acts on the metabolic response of energy conservation triggered when, for example, we are starving or dieting, science has important implications for understanding why it is very difficult to lose weight , "he said.

This work is part of the Thematic Project "Action of growth hormone in the nervous system: relevance for nerve function and disease", supported by FAPESP. Participants were researchers from the ICB, Ribeirão Preto Medical School at USP, La Plata National University in Argentina, and Ohio University in the United States.

"Science has been searching for decades to understand why it's so difficult to maintain weight after a successful diet sacrifice and why it's so easy to regain lost weight." To this day, leptin is considered as taking action to save energy when we are starving, "Donato said.

He explained that when there is weight loss, the levels of circulating leptin fall into the bloodstream. But such knowledge never results in the creation of a successful diet or leptin therapy which will cause patients to lose and maintain their weight.

"Obviously, the process of weight loss involves several metabolic processes and some hormones other than leptin." This is where GH comes in. We have identified that when GH loses weight, it works in the brain in a manner similar to leptin. , if in the case of leptin the level falls, in the case of GH the opposite occurs. "Weight loss triggers an increase in GH levels in circulation," said Donato.

"In the article now published, we have shown that, like leptin, central growth hormone signaling also promotes neuroendocrine adaptation during food shortages," he said.

The GH receptor is located in a brain region called the hypothalamus, which is considered the highest vegetative center of the brain. The hypothalamus starts impulses that affect nerve cells of the neurovegetative system and regulates visceral tissue, such as smooth muscle viscera and blood vessels, heart muscle, all glandular organisms and also the kidneys, among other organs.

The researchers observed that in the hypothalamus, the GH receptor specifically activates a small number of neurons called AgRP which in turn increases the production of homonym protein AgRP, which acts to increase appetite and reduce energy metabolism and expenditure.

"AgRP is one of the most effective appetite stimulators. It is interesting to note how the small population of AgRP neurons, which are several thousand in billions of neurons in the hypothalamus, perform important functions even though the number is reduced," said Donato.

To study in detail the importance of GH signaling in AgRP neurons, USP scientists and colleagues produced mice that stored AgRP-specific growth hormone receptor ablation (called KO AgRP GHR mice). Control groups with unmodified animals were also studied.

Among several other experiments, this group recorded energy expenditure in the entire body of two groups of mice when they were put on a 60% diet restricted diet. The aim is to examine whether the lack of adaptive responses to energy deficits will have a significant impact on energy balance.

It was observed that animals in the control group reduced their energy expenditure during food restrictions, which corresponds to an adaptive response that saves energy during such situations.

However, the decrease in energy expenditure in KO AgRP GHR mice during feed restriction was significantly lower compared to control mice, indicating that they did not save energy as efficiently as animals that had not been modified.

As a result, AgRP GHR KO mice showed a higher level of weight loss, mainly due to loss of fat mass, that is, fat reserves, but also because of the loss of the lean mass, that of all vital organs, bones, muscles, ligaments and tendons, and fluids body.

"In other words, we found that weight loss triggers an increase in the hormone GH in the hypothalamus, which activates AgRP neurons, making it harder to lose weight and increase hunger. Leptin," said Donato.

According to researchers, energy conservation is very important for the body so that evolution allows humans with two energy conservation mechanisms, one activated by leptin and the other by GH.

"One functions as a backup of the other. That's why all efforts to create weight loss treatments based solely on leptin have not been successful. You have to attack the growth hormone mechanism at the same time," said Donato.

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