One in 7,000: Scientists Discover Rare Genetic Variant That May Protect Against Obesity

Scientists have identified a rare genetic variant that may protect people from obesity and other metabolic disorders. The study, which analyzed genetic data from more than 1 million people, was published in the journal Nature.

Researchers examined data from 1,032,116 people from North America, Europe, and Asia. They searched for rare genetic changes associated with the ratio of triglycerides to “good” HDL cholesterol—a marker of metabolic health that is linked to the risk of obesity, insulin resistance, high blood pressure, and cardiovascular disease.

The scientists identified 59 genes involved in regulating energy metabolism, as well as fat storage and utilization. One gene in particular, FNIP1, attracted their attention. It appears to act as a kind of “brake” on energy expenditure by cells.

A rare variant of this gene occurs in approximately one in 7,000 people. It switches off one of the two copies of FNIP1 and, according to the study findings, is associated with a more favorable metabolic profile.

People carrying the variant had lower body weight and a lower proportion of body fat, healthier fat distribution, lower levels of triglycerides and “bad” cholesterol, as well as less fat accumulation in the liver.

In addition, their risk of cardiovascular and other cardiometabolic diseases was approximately 60% lower than that of people without the genetic variant.

To investigate the potential mechanism, the researchers switched off FNIP1 in human liver cells. This activated genes involved in breaking down fats and clearing cellular “waste.”

The researchers then conducted experiments in mice. Animals with the FNIP1 pathway switched off remained significantly more resistant to weight gain and fat accumulation in the liver, even when fed a diet high in fat and sugar.

The authors suggest that FNIP1 could become a promising target for future treatments for obesity, fatty liver disease, diabetes, and cardiovascular disease. However, developing such treatments will require further research, including studies in humans.

The findings also help explain why some people can maintain a relatively healthy weight and metabolism despite having similar diets to others: some of these differences may indeed be linked to rare genetic variants.