Researchers at the Regeneron Genetics Center in New York discovered a rare gene mutation that helps people burn more calories and stave off weight gain.
The study found that carrying a broken copy of Folliculin Interacting Protein 1, or FNIP1, alters how the body regulates cellular energy and metabolism. Normally, the FNIP1 gene controls how cells burn or store fuel.
However, about one in 7,000 people, or one million people worldwide, carry a faulty copy of the gene that causes the body to burn calories more easily without dieting or taking GLP-1 drugs.
The research team analyzed genetic data from more than one million participants across North America, Europe, and Asia. In total, researchers identified 150 participants who carried an FNIP1 mutation.
Participants with the FNIP1 mutation had lower blood sugar, decreased cholesterol, lower triglycerides, less liver fat, lower overall body fat, and a healthier distribution of fat. They also showed about a 60 percent lower risk of developing metabolic conditions such as obesity, type 2 diabetes, coronary artery disease, metabolic dysfunction-associated steatotic liver disease (MASLD), and liver cirrhosis.
This lower risk had nothing to do with classic weight loss measures like diet and exercise. Instead, carriers were simply burning more calories due to the genetic mutation.
"These individuals consume, store and utilize energy more efficiently than individuals without those mutations, and that's the protective factor," Luca Lotta, study co-senior author and geneticist at Regeneron Pharmaceuticals, told Scientific American.
"Nowadays, we are living in a very calorie-rich environment, and historically there's no precedent for this," Lotta said. "These incredibly rare mutations, which might have been unfavorable for many millennia, are now favorable to the body."
Testing cost and drug potential
About 48,000 Americans have the mutation, researchers estimate. The only way to conclusively determine if a person has the gene is to get genetic sequencing blood tests, which cost between $1,000 and $2,000 out of pocket depending on insurance.
The team said their work, published in the journal Nature, could help with the development of new weight loss drugs that mimic the effect of shots like GLP-1s.
In the study, scientists performed DNA sequencing on just over one million participants from major research cohorts, including the UK biobank database. They measured blood lipids such as cholesterol and triglycerides, blood sugar, blood pressure, and C-reactive protein, which measures liver inflammation levels.
The team also measured differences in participant body fat, muscle mass, and history of liver, kidney, and heart disease.
Mice studies and health risks
The researchers tested whether silencing FNIP1 in liver cells could turn on fat-burning genes. In mice fed a fatty, sugary diet, altering the gene curbed weight gain, reduced fat, and improved insulin sensitivity. Over 30 weeks, the treatment prevented liver scarring.
Notably, inheriting two broken copies of FNIP1 instead of just one did not have protective effects. Instead, it had the opposite outcome, increasing vulnerability to heart disease and immune deficiency.
"If you were to therapeutically inhibit the gene everywhere in the body at 100 percent, that could have a negative impact on health," Lotta said.
Lotta noted that targeting the gene in the liver may help mitigate those risks, but cautioned that any therapy is many years away.
