A Secret Hunger Switch in the Brain Uncovered

January 6, 2023

Summary: It is no secret that obesity runs in families. However, some people have difficulty controlling their appetite, and they eat most of the time, leading to severe obesity. Obesity not only leads to the problems of being overweight, but also advances towards serious issues such as diabetic neuropathy and other chronic pain. Researchers know this kind of more severe obesity results from a genetic defect. The new study found a secret hunger switch that malfunctions in these individuals. The switch called MC4 is located in the hypothalamus, and it is activated by default, thus sending signals not to eat more food. It only deactivates when the body needs energy. However, its malfunction causes severe hunger. A new drug called setmelanotide can help reactivate this switch and thus prevent the continuous urge to eat.

Obesity is a considerable problem in developed economies like the US. However, some cases of obesity are special. Some individuals just can’t stop eating. It is quite often true when obesity runs in families. It appears that in some people, the brain just fails to regulate appetite. Therefore, there are people who keep eating all the time, and they never feel satiety. They are never satisfied with what they eat and how much they eat. Experts have long known that these are people genetically prone to obesity.

However, knowing the genetic defect leading to uncontrolled appetite is not enough. It is vital not to know about the genes involved but the exact mechanism that leads to an unchecked appetite. It seems that researchers have discovered a secret switch in the brain which is responsible for controlling appetite.

In a study published in the journal Science, researchers from multiple universities, who worked on the subject, revealed their findings. They found that melanocortin receptor 4 or MC4 played a critical role in controlling human appetite and almost acted as a switch. But unfortunately, this also means that this switch starts malfunctioning in those with insatiable appetites.

These are new findings, and they can significantly help treat obesity. First, it improves our understanding of how our body regulates appetite. In fact, one of the drugs approved for insatiable appetite and fight obesity called setmelanotide (Imcivree) works by acting on this switch. Researchers noticed many interesting things about how this switch operates. First, it is located in the brain region called the hypothalamus. There is a cluster of neurons in the hypothalamus that act as a switch. These neurons constantly keep analyzing the body’s energy balance.

It is interesting to note that if these neurons sense sufficient energy supply, they keep the MC4 switch activated or “on.” This tells the brain and the body to feel full and not to eat more. It also means that this “on” status is the default setting. Hence, this switch remains activated most of the time.

This also means that people feel hungry or urge to eat when this switch is turned off or MC4 receptors are deactivated. However, these receptors remain deactivated only till the person has eaten sufficiently. After this, the brain or certain neurons again activates this switch, thus sending a signal to stop eating. Hence, this brings our body back to its default setting, which is a high satiety state.

However, it appears that this switch is not working properly in some individuals. Studies show that in such individuals, the new drug setmelanotide can reactivate this switch, thus helping them reduce their appetite or urge for food.

This new study began when researchers studied a family of eight members who had an insatiable appetite. In addition, all of them had a BMI above 70. Thus, they knew that these people or families differ, and there is surely some genetic defect in these individuals. This research was the subject of the Ph.D. study of one of the students at the Hebrew University of Jerusalem. However, since the topic was complex, the research was done in collaboration with multiple research centers, including some UK-based institutions.

Moreover, advanced equipment in some of these centers, like an electron microscope, helped understand the structure of this secret hunger switch. Researchers carried out multiple experiments, and now they know almost exactly how this switch works. Hence, in the future, we are likely to see the introduction of more drugs that can not only reactivate this switch but also prevent its malfunction.

The Takeaway

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By Gurpreet Singh Padda, MD, MBA, MHP