Saturday , January 16 2021

Growth hormone acts to prevent weight loss

A group of researchers at the University of São Paulo (USP) in Brazil found that growth hormone (GH), linked to bone development and height increase, also acts directly on the brain to conserve energy when you lose weight.

This finding was published in the journal Nature Communications. "We discovered that a hormone known for decades does much more than was imagined," said José Donato Junior, a professor at the Institute of Biomedical Sciences (ICB) at USP and one of the authors of the study that has the support of the research. Foundation for Scientific Research Support of the State of São Paulo – FAPESP.

"GH receptors are present in large amounts in the muscles, liver, tissues and organs directly involved in growth metabolism, but we found that the brain is also full of GH receptors," said Donato.

"And we also find that GH in the brain does not only participate in growth metabolism, but that it acts fundamentally in the metabolic responses of energy conservation that are triggered when we starve or make regime, for example. science, has important implications for understanding why weight loss is so difficult, "he said.

This work is part of the Thematic Project titled "The action of growth hormone in the nervous system and its relevance to neural functions and diseases", supported by FAPESP. Among the participants are researchers from ICB, USP's Ribeirão Preto Medical School, the National University of La Plata in Argentina, and the University of Ohio in the United States.

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On the right, AgRP neurons from animals knocked out to the GH receptor; to the left, control animal neurons. (Photo: Communications from nature)

"Science tries to understand for decades why it is so difficult to maintain the weight that is achieved after the sacrifices involved in making a successful diet and why it is so easy to regain lost weight.However, leptin was believed to be the major hormone which goes into action to conserve energy when we starve, "Donato said.

The researcher explains that when weight loss occurs, leptin levels circulate in the bloodstream. But this knowledge never resulted in the successful development of a diet or leptin treatment that would lead patients to lose weight and maintain their weight.

"The process of weight loss clearly encompasses several metabolic processes and involves the action of several hormones, not just leptin." And that's when GH comes in. We found that when weight loss occurs, GH acts in the brain in a similar way However, although in the case of leptin their levels drop, in the case of GH the opposite happens. Weight loss triggers the elevation of circulating levels of GH, "said Donato.

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

GH receptors are located in an area of ​​the brain called the hypothalamus, which is considered the highest of the vegetative centers of the brain. From the hypothalamus, there are impulses that influence the nerve cells of the neurovegetative system that regulate the visceral tissues, such as the smooth muscles of the viscera and vessels, the cardiac musculature, all the glands of the organism and even the kidneys, among other organs.

The researchers observed that in the hypothalamus, GH receptors specifically activate a small population of neurons called AgRP, which in turn increases the production of the homonymous protein AgRP, which acts to increase appetite and decrease metabolism and hormone expenditure . energy

"AgRP is one of the most potent stimulants of appetite. It is curious to note how a small population of AgRP neurons, a few thousand units, in the midst of billions of neurons in the hypothalamus, plays such an important role despite its small numbers," he said. Donato.

To study in detail the importance of GH signaling in AgRP neurons, USP scientists and their peers generated mice that removed AgRP-specific growth hormone receptors (called AgRP GHR KO mice). A control group was also studied with unmodified animals.

Among other experiments, the group recorded energy expenditure throughout the body of both groups of mice when they were submitted to a 60% dietary restriction diet. The purpose of this was to test whether the lack of adaptive responses to energy deficits would cause significant impacts on the energy balance.

It was observed that the animals in the control group decreased the energy expenditure during the food restriction, which is in agreement with the adaptive responses that conserve energy during the said situation.

However, the decrease in energy expenditure in AgRP GHR KO mice during feed restriction was significantly lower in comparison to control animals, suggesting that the former did not conserve energy as efficiently as unmodified animals.

Consequently, the AgRP GHR KO mice had a higher rate of weight loss, predominantly due to the loss of fat mass, that is, fat reserves, but also due to the loss of lean mass, which consists of all vital organs: bones, muscles , ligaments and tendons, and body fluids.

"In other words, we found that weight loss triggers an increase in the levels of the GH hormone in the hypothalamus, which activates the AgRP neurons, making it difficult to lose weight and increase the sensation of hunger.This is exactly the same function as leptin "said Donato.

According to the researcher, energy conservation is so important to the body that evolution trained humans with two mechanisms of energy conservation: one activated by leptin and the other by GH.

"One works as a reserve for another, which is why all attempts to develop leptin-based weight loss treatments have not yielded results," said Donato. "The growth hormone mechanism must be attacked at the same time." (Source: AGENCY FAPESP / DICYT)

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