Understand The Cause
Acquired HO starts in the brain
The hypothalamus is the brain’s control center for hunger, calorie use, and weight
The hypothalamus is a small but important part of the brain that helps regulate many important bodily functions related to weight.
Hunger and
fullnessTelling your body when and how much to eat
Hypothalamus
Calorie useTelling your body to use or store energy
Body weightBalancing food intake and calorie use to keep weight stable
The hypothalamus sends and receives signals using different pathways in the brain. A key pathway for signals about hunger, fullness, and calorie use is called the MC4R pathway (or the melanocortin-4 receptor pathway).
How acquired HO affects the body
Acquired hypothalamic obesity (acquired HO) happens when specific messages between the body and the brain stop working.
Like cars on a highway, messages in the body travel along the MC4R pathway
When the MC4R pathway is working, messages about fullness and calorie use reach their destination. These messages help the brain know how to regulate body weight.
With acquired HO, the MC4R pathway is damaged
A damaged MC4R pathway means messages about fullness and calorie use don’t get through. Without those messages, the brain thinks the body’s not getting enough food and keeps telling the body to eat food and store calories.
Symptoms can be more or less severe depending on how much and what part of the hypothalamus is injured. Usually, weight gain is rapid and sustained, even with diet and exercise.
Why diet and exercise aren’t enough
Gaining or losing weight isn’t just about food consumption. It’s also about how the body uses calories—called energy expenditure.
Most of your energy expenditure is for essential functions like breathing, pumping blood, and staying warm. With acquired HO, metabolism can slow down. The body uses fewer calories for essential functions each day and stores unused calories as fat. This change in metabolism is not something you can control.
The impact of decreased energy expenditure in acquired HO
Before Acquired HO Stable weight
Brain tells body:UseAllof your consumed
daily calories
With Acquired HO weight gain
Brain tells body:UseFewerthan all of your
daily calories
Unused calories
are stored as fat
With acquired HO, you can eat the same amount of food as you did before—or even less—and still gain weight.
Constant hunger makes it even harder to manage weight
For people with constant, hard-to-control hunger, eating more can contribute to weight gain. Combined with the body using fewer calories than expected, this is why weight gain in acquired HO can be both rapid and hard to reverse.
Living with acquired HO can feel overwhelming, but you’re not alone.
A Rhythm Patient Education Manager (PEM)* can answer questions and help you access educational resources tailored to your personal needs.
Patient Education Managers are employees of Rhythm Pharmaceuticals and do not provide medical care or advice. We encourage you to always speak to your healthcare providers regarding your medical care.