From anorexia to obesity
A hunger molecule regulating weight has been found
Daniil Sukhinov, Naked Science
Scientists from Yale University have discovered that the protein augmentor-alpha, known for its connection with some cancers, is able to regulate body weight, affecting hunger and physical activity. This discovery will allow the development of new treatments for metabolic disorders such as obesity and anorexia.
Augmentor is an alpha protein known primarily for its association with the development of certain types of cancers. Earlier studies have shown that this protein binds to and activates the anaplastic lymphoma kinase receptor (ALK), a molecule that, when mutated, causes cancers such as pediatric neuroblastoma, B—cell lymphomas and some lung cancers.
The research team decided to take a closer look at augmentor-alpha and its role in the body. During experiments on mice, scientists found that this protein is most strongly expressed in the hypothalamus region of the brain, namely, in cells called agouti—related peptide neurons (agouti-related peptide, AgRP).
"AgRP neurons are so important for the formation of hunger that without them you simply would not eat. You would have died," explains Tamas Horvath, professor of comparative medicine at the Jean and David Wallace Foundation and co—author of the study. "Therefore, when it became clear that augmentor—alpha was predominantly expressed in these neurons, we immediately assumed that it was involved in metabolism."
In addition, the team found that fasting increases the expression of the augmentor-alpha protein in these neurons. In addition, if mice completely disable the possibility of synthesizing this molecule, they lose weight noticeably, regardless of the fat content in the food they eat. At the same time, the physical activity of such mice was even higher than normal, which probably contributed to their thinness.
According to the researchers, when faced with a lack of food, mice usually save energy and reduce physical activity. But during fasting, rodents without the augmentor-alpha protein were still very active, although they ate exactly the same as ordinary animals. This means that this protein acts as an important signal for energy conservation and the formation of hunger.
"Based on what we observed in this study, we think that one of the roles of the augmentor-alpha protein in the body is to slow down metabolism with a lack of food," comments Professor Joseph Schlessinger, director of the Yale Institute of Cancer Biology and lead author of the study. — The protein seems to say, "You don't have food, don't waste so much energy."
According to the authors of the study, this connection with metabolism suggests that suppressing or enhancing the effect of the augmentor-alpha protein may be useful in a number of diseases. Drugs that inhibit protein synthesis — as some cancer drugs targeting ALK do — may be reassigned to treat metabolic disorders leading to overweight. And enhancing the effect or expression of this molecule can be one of the treatment options for people experiencing excessive weight loss: for example, suffering from anorexia, cachexia or permanent loss of appetite due to side effects of medications or injuries.
The results of the study are published in the journal Proceedings of the National Academy of Sciences (Ahmed et al., A hypothalamic pathway for Augmentor α–controlled body weight regulation).
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