A closer look at insatiable hunger

Welcome, and thanks for joining us for “Why am I so hungry? Understanding insatiable hunger.” I'm Jill Garrison, and I'm on the Medical Affairs team at Rhythm Pharmaceuticals. Rhythm is a small biopharmaceutical company that was founded in 2008, and is located in Boston, Massachusetts. At Rhythm, we're dedicated to transforming the care of individuals living with rare genetic disorders of obesity.

My personal background is in scientific research. I earned my Ph.D. in nutritional and metabolic biology, and for the past 15-plus years, I've been studying how the brain regulates body weight and our metabolism. And related to this, I have studied how there are many different factors that can disrupt this body weight regulation and ultimately lead to obesity and its related health consequences.

There are many different rare genetic disorders of obesity, and they present in many different ways, but they often present with two common symptoms: severe obesity that occurs early in life, also known as early-onset obesity, and a feeling of insatiable hunger, also known as hyperphagia.

Today, we're going to take a closer look at why this happens in individuals with rare genetic disorders of obesity. We'll take a look at what insatiable hunger looks and feels like, how hunger works in our bodies, and what happens in someone with a rare genetic disorder of obesity.

Let's take a closer look at insatiable hunger. Insatiable hunger, or hyperphagia, is different than regular hunger. Insatiable hunger is a deep hunger that doesn't go away. It feels like your body is always hungry, and your hunger is stuck in the “on” position. And because of this, it can make it difficult to focus, because you are constantly consumed by the desire to eat. One mom describes what this is like for her son:

“His hunger started at one week. He cried of hunger all the time. He hurt. He will live his whole life hungry. Hunger controls him.”

While different in each person, insatiable hunger often causes:

• Intense hunger that doesn't go away
• Taking a longer time to feel full while eating
• Feeling hungry again right after a meal
• Thinking about food constantly
• Becoming very upset when food is unavailable
• Always looking for food. For example, this could include stealing food, waking up at night to find food, or even eating food others leave behind, or from the trash.

The feeling of insatiable hunger can be overwhelming. Another mom describes it:

“My daughter has told me, 'I know you are going to feed me, but it's like I'm battling with my mind.' It's a struggle.”

So what causes insatiable hunger? 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.

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.

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.

So, to recap, rare genetic disorders of obesity may be caused when the MC4R pathway in the brain isn't working properly. In this case, our brain instructs our body to keep eating, even if we already have just eaten. When this happens, it can lead to severe obesity early in life, and insatiable hunger.

I hope you found this helpful. If you suspect you have a rare genetic disorder of obesity, or know someone who does, we encourage you to check out our LEAD website, at LEADforRareObesity.com, for additional resources. Here you can sign up to receive updates, or find helpful tools, such as a doctor discussion guide, or information about our genetic testing program. This video is one of a series, and so we hope you'll check back on Facebook again to find when the next video posts.

Thanks for watching.

LEAD for Rare Obesity is an initiative of Rhythm Pharmaceuticals, Inc.
© 2019 Rhythm Pharmaceuticals, Inc. All rights reserved. MC4R-C0281-10.2020