Hunger so overwhelming it can't be tuned out
For a rare few, insatiable hunger may make it feel as if your brain is constantly whispering in your ear, telling your body that you’re hungry. Often, it can feel like that voice has no “off” switch. This feeling may be caused by a rare genetic disease of obesity.
Common symptoms of rare genetic diseases of obesity

Severe obesity early in life
Children, from early infancy up to the age of 10, may gain far more weight than would be expected for their age. This is called early-onset obesity.

Insatiable hunger
There may be overwhelming feelings of hunger—a deep hunger that can make it difficult to think about anything else—no matter the time of day, even just after meals. Take a closer look >
The science of hunger
Did you know hunger isn’t just triggered by your stomach? It also involves your brain.
There are specific parts of your brain that control hunger by sending signals to your body, telling it when to eat and when to stop.

In rare genetic diseases of obesity, genetic variantsVARIANT Genetic variants may result in serious health problems or be "silent" with no negative health effects. interrupt these messages and hunger gets stuck in the "on" position.
How hunger works in our bodies
How does hunger work?
How does hunger work in our bodies? Let’s take a closer look.
To understand the science behind it, let’s take a look at what hunger looks like in all of our bodies.
Simply put, we need energy to live. Our bodies need fuel in order to go about our daily lives, in order to perform the functions it needs to stay alive, and we get this energy, we get this fuel, from food.
So our body has many systems in place to make sure that we consume the right amount of food, the right amount of energy to go about and live our daily lives. And when this system is functioning properly, when we are eating as much energy as we are using it to live our lives, this system is in balance and our body weight stays stable, it stays in balance.
When we eat too much food, when we eat more food than our body actually uses in its daily lives, our bodies end up storing this energy as fat tissue, and this is when weight gain occurs.
Now the opposite is also true, if we eat too little food, if we don’t eat enough energy, we don’t have the fuel our body needs to go about and live our daily lives.
Our bodies have natural checks and balances to make sure this balance stays even. We have triggers in our body that tell us when to start eating and when to stop, and hormones act as the messengers.
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Rhythm, LEAD for Rare Obesity, and their logos are trademarks of Rhythm Pharmaceuticals, Inc.
© 2020 Rhythm Pharmaceuticals, Inc. All rights reserved. MC4R-C0281(E)-04.2020
The brain-body connection
Our bodies have several processes to balance the food we take in throughout the day with the energy we need to function.
When your stomach is empty, a signal is sent to your brain. Your brain then releases a protein to kickstart your appetite.
Once your stomach is full, a different message is sent to your brain. Your brain then dials down the protein to decrease your appetite and turns up one that is an appetite suppressant.
How do our bodies stay balanced?
Now let’s take a closer look at what we can call the “I’m hungry”cycle.
Now, imagine an empty stomach with no food in it. Basically, representing a body that is low on energy and needs fuel. When this happens, hormones from the body report this low status to the brain, sending the message of, “I’m empty, eat something.” The brain gets this message and in turn, releases a protein to stimulate the appetite.
The opposite also occurs when we have the “I’m full” cycle. Once there is food in the stomach, representing a body that has enough energy, a message is sent to the brain telling it, “I’m full, stop eating.” The brain then goes ahead and dials down that protein that stimulated the appetite and cranks up the one that is an appetite suppressant so that the person stops eating.
For more videos like this, don’t forget to check back on our Facebook page and at LEADforRareObesity.com.
Rhythm, LEAD for Rare Obesity, and their logos are trademarks of Rhythm Pharmaceuticals, Inc.
© 2020 Rhythm Pharmaceuticals, Inc. All rights reserved. MC4R-C0281(F)-04.2020
Making sense of the signals
There are many parts in the brain that communicate with each other to regulate hunger. One of these areas is called the melanocortin-4 receptor, or MC4R pathway. Think of it like a road carrying news and information to and from the brain.
When this pathway works the way it should, the brain receives a message that it’s time to stop eating. In rare genetic diseases of obesity, part of this pathway is broken, and the body and brain can’t communicate to each other properly. The brain doesn’t get the message when the stomach is full and believes that the body is starving, even though the body has had enough food.
The brain’s hunger pathways
So, how do our brains make sense of all these messages telling it to eat something, or stop eating?
How does it know when to send those appetite stimulating, or suppressing signals?
The specific part of our brain that accepts these messages, and makes sense of them, is called the hypothalamus. Think of the hypothalamus as a neighborhood within the brain. In this neighborhood, there is a road called the MC4R pathway.
On this road, cars travel carrying news and information, to and from the brain. These cars on the MC4R pathway are proteins and hormones that communicate with each other to control hunger, and regulate our energy balance.
In individuals with a rare genetic disorder of obesity, this process does not work as it should. A genetic variant, or a change in the body’s DNA, causes part of this pathway to not work properly.
Think of one of the roads as blocked, and the cars can’t get through. When this happens, the signals in the hypothalamus get stuck in the “I’m hungry” cycle, because the “I’m full” message cannot get through and be delivered. The brain doesn’t get this message and believes that the body is starving, even though there is food in the stomach. Without this message or signal, this can cause insatiable hunger and ultimately lead to extreme weight gain early in life.
For more videos like this, don’t forget to check back on our Facebook page and at LEADforRareObesity.com.
Rhythm, LEAD for Rare Obesity, and their logos are trademarks of Rhythm Pharmaceuticals, Inc.
© 2020 Rhythm Pharmaceuticals, Inc. All rights reserved. MC4R-C0281(C)-01.2020
Learn more about some of the many different rare
genetic diseases of obesity
MOM TO JOSHUA, LIVING WITH A SUSPECTED RARE GENETIC DISEASE OF OBESITY
The role of genetics

Genes
Genes are your body’s instruction manual. They determine how your body grows, develops, and functions.
Genes are passed down to you from your parents. While genes can determine obvious traits like eye color and hair color, they are also responsible for genetic conditions like rare genetic diseases of obesity.
We have two copies of most of our genes—one from our mother and one from our father. All of us have changes in our genes, called variants, which make us unique. Not all genetic variants cause diseases, but some can.
Sometimes you need two copies of a certain gene – one from your mother and one from your father – to result in disease. Other times, just one will cause disease.
Occasionally, a gene for a rare condition will be present in both the mother and the father. When they have a child, that child may inherit two copies of the disease-causing (pathogenic) variant. If the child develops symptoms of the condition, the condition is called an autosomal recessive (AR) condition. Many rare genetic disorders of obesity are passed down from the parents to their child in this AR pattern.
You can carry a gene but not be affected
If you have only one copy of the gene with a disease-causing variant, you are considered a carrier but will generally not have any symptoms of the disease.
If both parents carry the gene for a disorder, each child they conceive will have:
Genetic predisposition vs genetic variants
While rare genetic diseases of obesity are caused by disease-causing gene variants, there are other forms of obesity that appear to run in families, but do not follow a predictable pattern or have the same early and severe symptoms.
Two ways that you can inherit obesity from your parents are:
- A genetic predisposition to obesity, or
- A genetic variant that causes obesity
Having a genetic predisposition to obesity means that you are more likely to develop obesity than people with a different genetic makeup. Although obesity may run in your family, it doesn’t mean you will develop obesity. Other factors like diet, activity level, and even where you live can influence whether or not you develop obesity.
Inheriting a genetic variant that causes a rare genetic disease of obesity is different from a genetic predisposition. If you inherit a specific gene variant, you are likely to develop obesity, even if you change your lifestyle or environment.