Obesity is often linked to serious health problems like heart disease and high cholesterol.
But a new study has found something surprising: people who are obese due to a rare genetic condition might actually have better heart health than expected.
The research, published in Nature Medicine, focused on people with a specific gene mutation called MC4R deficiency.
MC4R stands for melanocortin 4 receptor, a gene that helps control body weight by regulating appetite and energy use.
When this gene doesn’t work properly, it can lead to severe early-onset obesity. However, the study found that people with this condition also had lower cholesterol, lower triglyceride levels, and a lower risk of heart disease—even though they were obese.
The researchers looked at the genetic data of 7,719 children from the Genetics of Obesity Study (GOOS). They identified 316 children and 144 adult relatives who had obesity due to MC4R gene mutations.
They compared these individuals to over 336,000 people in the UK Biobank who didn’t have the mutation. Surprisingly, those with MC4R deficiency had better blood pressure and heart health, even after adjusting for their weight.
To understand why, the team took a closer look at how the body processes fat. Normally, obesity is linked to high levels of harmful fats in the blood, like LDL cholesterol and triglycerides, which raise the risk of heart disease.
But the MC4R-deficient group had a healthier fat profile. The scientists believe this is because the brain, which controls many body systems, plays a bigger role in fat metabolism than previously thought.
The researchers ran three types of tests. First, they examined people with MC4R-related obesity in a clinical setting. Then they checked their findings in a much larger group from the UK Biobank. Finally, they conducted a small experiment where participants ate a high-fat meal, and the team tracked how their bodies processed the fat.
In this meal test, 11 people with the MC4R mutation were compared to 15 people of similar age, weight, and health status. The researchers found that those with the mutation processed fat differently. They had fewer harmful fat particles in their blood after eating and showed lower inflammation and better blood pressure.
This study changes how we think about obesity and heart disease. It suggests that not all forms of obesity carry the same risks, and that some people may have genetic protections that keep their hearts healthier.
The researchers say the MC4R pathway could become a new target for heart disease treatments. If scientists can create drugs that copy the protective effects of this gene mutation, it might help more people lower their risk of heart problems—even if they don’t lose weight.
In conclusion, this research offers hope for new ways to treat heart disease. It highlights the complex role of genetics in obesity and shows that better heart health may not always require major weight loss. Future therapies could focus on how the body processes fat, not just how much fat a person carries.
If you care about heart disease, please read studies about a big cause of heart failure, and common blood test could advance heart failure treatment.
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The study is published in Nature Medicine.
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