Genetics and Obesity

The link between genetics, hard-to-control hunger, and obesity

While many people experience hunger and weight gain, in a very small number of people, hard-to-control hunger (which can be referred to as hyperphagia) can be because of a problem in an area of your brain (called the hypothalamus), caused by your genes.1

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Melanocortin-4 receptor pathway signals as dominoes

All living things are made up of basic building blocks called cells. Our cells have something called ‘genes’ in them. These genes are an instruction book for your body. Sometimes genes can have small errors, like a spelling mistake in the instruction book.2

When this happens, the signals that turn hunger “off” don’t work correctly in the brain. This can lead to hard-to-control hunger and then obesity.3

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Genetic and obesity
The melanocortin-4 receptor pathway

In the brain, the hypothalamus carries important signals about the rest of the body. We can think of each signal as a chain of upright dominoes waiting to fall. One of these chains, called the ‘melanocortin-4 receptor’ or ‘MC4R’, pathway, is important for controlling feelings of hunger.

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The melanocortin-4 receptor pathway

Some of the dominoes in the MC4R pathway chain represent genes, and each one knocks into the next to send a message in the brain that the body doesn’t need any more food.3

When these genes work normally, all the dominoes are in place, and fall for the signal to be received by the brain.1 

But if you remove a domino, or gene, from the chain, there is a gap, and the message isn’t received, as the dominoes stop falling when they reach the gap. As a result, the body believes it is still hungry. When this happens, doctors may say someone is living with a rare MC4R pathway disease.1

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Melanocortin-4 receptor pathway signals as dominoes
A gap in the chain

In people living with rare MC4R pathway diseases, one or more of these dominoes are missing due to the change in the relevant gene. When this happens, the brain doesn’t know that the body is satisfied and doesn’t need more food. Instead, the brain thinks the body is still hungry, which can contribute to someone developing obesity. A gap in the chain of dominoes, or impaired MC4R pathway, is a root cause of hard-to-control hunger and obesity in these diseases.1

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Melanocortin-4 receptor pathway signals as dominoes

A doctor may think there is a genetic cause of someone’s hard-to-control hunger and obesity, and they may want to test the genes in the MC4R pathway to see if they are different. The important thing to remember is that this isn’t anyone’s fault.

What can you do?

If you think you have spotted one or more of these signs in yourself, or your child, download and complete our discussion guide to help prepare for an appointment with your doctor or nurse.

References

1 Adan RAH, et al. Br J Pharmacol. 2006; 149(7): 815–827

2 Genetic Alliance; The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services. Understanding Genetics: A New   
York, Mid-Atlantic Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2009 Jul 8. APPENDIX A, BASIC   
GENETICS INFORMATION. Available from: https://www.ncbi.nlm.nih.gov/books/NBK115558/

3 Eneli I, et al. Appl Clin Genet. 2019; 12: 87–93