When we find ourselves in distress, the body knows how to silence all the processes that are not essential, and allocate the most resources to the processes that are more necessary at that time. But is there a connection between distress situations and the body's metabolism? Weizmann Institute of Science scientists examined the behavior of mice in stressful situations, and discovered that the receptor that allows the body to respond to these situations has an additional role
When we find ourselves in distress, the body knows how to silence all the processes that are not essential, and allocate the most resources to the processes that are more necessary at that time. But is there a connection between distress situations and the body's metabolism? Weizmann Institute of Science scientists examined the behavior of mice in stressful situations ("stress"), and discovered that the receptor that allows the body to respond to these situations has an additional role in this context. Their findings, which may help in the future in the development of more effective drugs for the treatment of metabolic disorders or eating disorders, were published recently in the scientific journal Cell metabolism.
The research began as part of the doctoral thesis of Dr. Yael Kuperman, then in the laboratory of Prof. Alon Chen from the Department of Neurobiology, and currently a faculty scientist in the Department of Veterinary Resources. Dr. Kuperman, Prof. Chen and research student Mayra Weiss focused on the area of the brain called the "hypothalamus", which is responsible for the regulation of many processes, including the body's dealing with stressful situations and the regulation of eating, the glucose economy and energy expenditure.
During distress, a protein is secreted in the hypothalamus, which activates a receptor called CRFR1. It is known that this receptor itself contributes to the activation of the sympathetic nervous system, which activates an immediate response when the body is under stress. In fact, in this area, which regulates the metabolism in the brain, there are many receptors of this type, but until now it was not clear what exactly their role is, and in which cells they are expressed.
To answer these questions, Prof. Chen and the members of the research group he heads characterized the cells in the studied area of the hypothalamus, and discovered that it is expressed in about half of the cell population that encourages eating and suppresses energy expenditure. It is one of two main populations of cells found in this area of the hypothalamus; Regarding the second group, it is known that it encourages satiety and energy expenditure. "It was a surprise," says Dr. Cooperman. "Intuitively, we would expect the receptor to be expressed in cells that suppress hunger, because in stressful situations, in many cases, animals and humans stop eating."
To test this aspect, the scientists removed the CRFR receptors1 Only fits that encourage eating in the hypothalamus in laboratory mice, and check how the change affects the functioning of their body. Although at first no substantial change was recorded, since the receptor is activated in stressful situations, the scientists exposed the mice to stressful situations - cold and lack of food - and tested them afterwards.
As for cold conditions, in general, in such a situation the sympathetic system activates the warm fat tissue in an increased way in order to protect the body temperature, and this is done through heat production (in the past it was common to think that in humans this tissue only plays a role in the first months of infancy, to maintain the baby's body temperature, but nowadays it is clear that it also plays a role in adults). If so, in a normal state, this tissue is responsible for stabilizing the body temperature. But in the abnormal state created in this study, due to the removal of the CRFR receptors1From the body of the mice, following their exposure to the cold, their body temperature dropped significantly, and did not return and stabilize afterwards. In contrast, no significant change was observed in male mice.
Even under fasting conditions, a similar reaction was observed in females. In a normal situation, when there is a lack of food, a signal is sent from the brain that signals the liver to produce glucose, thus maintaining a normal level of blood sugar. But when food is withheld from the mice lacking the CRFR receptors1, the amount of glucose produced by their liver decreased significantly. As for the male mice, similar to their exposure to cold, in this case too the absence of CRFR receptors did not cause1 to undermine the metabolism in their body.
"We discovered that the receptor has an inhibitory role in the cells that prevent the activation of the sympathetic nervous system," says Dr. Kuperman. Prof. Chen adds: "It is important that these cells are inhibited in stressful situations, so that the body knows how to respond correctly to these situations."
In addition to understanding how this receptor works, and its meaning in stressful situations, the research revealed differences between the metabolic processes that take place in males and those that take place in females. As mentioned, the receptor suppresses the feeling of hunger in females, and it is possible that this mechanism may shed new light on the biological processes that cause the development of eating disorders, which are more common among women than among men.
This discovery may also help in the development of drugs designed to regulate hunger, especially because this process takes place in the hypothalamus, which is an area of the brain that is relatively accessible to blood circulation. A number of pharmaceutical companies are currently making attempts to develop psychiatric drugs that will block the function of the CRFR receptor1 - with the aim of causing a reduction in anxiety disorders or depression. At the same time, the scientists point out that manipulations of the same receptor may cause side effects that will disrupt the metabolism, and therefore may lead to obesity.
