Summary: The switch is called MC4, and it sits in the hypothalamus. It is on by default, and when it is on, it tells you to stop eating. It only turns off when the body needs energy. When it breaks, hunger runs wild. A new drug called setmelanotide can turn the switch back on and stop the nonstop urge to eat. Everyone knows obesity runs in families. But some people have trouble controlling their appetite. They eat most of the time and become severely obese. Obesity does more than add weight. It moves on to serious problems such as diabetic neuropathy and other chronic pain. Researchers know this severe kind of obesity comes from a genetic defect. The new study found a secret hunger switch that fails in these people.
Obesity is a huge problem in rich countries like the US. But some cases are special. Some people just can’t stop eating. This is often true when obesity runs in families. It appears that in some people, the brain simply fails to control appetite. So they eat all the time and never feel full. They are never satisfied, no matter what or how much they eat. Experts have long known these people are born prone to obesity.
But knowing the broken gene is not enough. We also need to know the exact chain of events that lets appetite run unchecked. Researchers now seem to have found a secret switch in the brain that controls appetite.
Researchers from several universities published their findings in the journal Science. They found that the melanocortin 4 receptor, or MC4, plays a key role in controlling human appetite. It works almost like a switch. The bad news is that this switch breaks down in people whose appetite is never satisfied.
These new findings could significantly help treat obesity. First, they show how the body controls appetite. In fact, one drug approved to treat nonstop hunger and fight obesity, setmelanotide (Imcivree), works on this switch. Researchers learned a lot about how the switch works. It sits in a brain area called the hypothalamus. There, a cluster of nerve cells (neurons) acts as the switch. These neurons keep checking the body’s energy balance, nonstop.
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.
So people feel hungry when this switch is turned off, meaning the MC4 receptors are shut down. But the receptors stay off only until the person has eaten enough. Then certain neurons turn the switch back on and send the signal to stop eating. That returns the body to its default setting: full.
But it appears that in some people, this switch does not work right. Studies show that in these people, the new drug setmelanotide can turn the switch back on. That helps them cut their appetite and their urge to eat.
This new study began with a family of eight who could never get full. Every one of them had a BMI above 70. So researchers knew this family was different and had to carry a genetic defect. The work was the Ph.D. project of a student at the Hebrew University of Jerusalem. Because the topic was complex, several research centers joined in, including some in the UK.
Some of these centers had advanced tools, like an electron microscope. Those tools helped reveal the shape of this secret hunger switch. Researchers ran many experiments. Now they know almost exactly how the switch works. So we will likely see more drugs that turn the switch back on and keep it from breaking.
The Takeaway
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Appetite control like this is one reason we treat weight as a medical problem in our physician-led weight loss program.
Frequently asked questions
What part of the brain controls hunger?
The hypothalamus. A cluster of neurons there keeps reading the body’s energy balance and works like a switch. The key part of that switch is the melanocortin 4 receptor, or MC4. When those neurons sense enough energy, they keep MC4 on. That tells the brain and body to feel full and stop eating.
What does the hunger switch do?
Its default setting is on, and on means full. MC4 stays active most of the time and signals that you do not need more food. It turns off only when the body needs energy, and that is when you feel hungry. Once you have eaten enough, the neurons switch it back on and the body returns to its normal state of satiety.
What happens when the hunger switch malfunctions?
The fullness signal fails. People with a faulty MC4 switch never feel full. They eat most of the time and become severely obese. This kind of obesity often runs in families because it comes from a genetic defect. The study began with a family of eight who all had a BMI above 70. Obesity this severe moves on to diabetic neuropathy and other chronic pain.
Is there a drug that fixes the hunger switch?
Yes. Setmelanotide, sold as Imcivree, is approved for nonstop hunger and works right on MC4. In people whose switch is broken, it can turn the switch back on and cut the constant urge to eat. Researchers now know the switch’s shape in detail. So more drugs that turn it back on or keep it from breaking are expected.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
