Scientists have identified a rare genetic mutation that causes approximately one in 7,000 people to naturally maintain a slender physique by burning calories at a higher rate. This discovery, published in the journal Nature, could pave the way for new therapeutic approaches to weight management and related health conditions.
The research, involving genetic data from over a million individuals across three continents, focused on the FNIP1 gene. This gene evolved to slow calorie burning when food is abundant, storing energy for times of scarcity. However, in individuals with the identified mutation, the FNIP1 gene is effectively turned off, leading to faster calorie expenditure rather than energy storage.
"Nowadays, we are living in a very calorie-rich environment, and historically there’s no precedent for this," Luca Lotta, a senior author on the study, told Scientific American. "These incredibly rare mutations, which might have been unfavorable for many millennia, are now favorable to the body."
Individuals carrying one copy of this deactivated FNIP1 gene variant were found to have lower body weight, reduced body fat, and less liver fat, alongside increased lean muscle mass. Beyond weight management, these individuals also experience significant health advantages, including lower cholesterol levels and a drastically reduced risk of developing conditions such as heart attack, stroke, kidney disease, and non-alcoholic fatty liver disease.
Researchers also explored the effects of this mutation in mice. By deactivating a copy of FNIP1, the mice demonstrated increased metabolism, protection against weight and fat gain, greater lean muscle mass, improved insulin sensitivity, and reduced liver fat. These findings suggest a potential for therapeutic interventions, although researchers caution that human applications are many years away and safety remains a key consideration.
While gene reprogramming for weight loss shows promise in animal models, the researchers noted that human gene therapy carries different implications than pharmaceutical treatments. Unlike drugs like GLP-1 agonists, which can be discontinued by patients if adverse effects arise, gene therapy is a more permanent intervention. The study indicates that disabling both copies of the FNIP1 gene can lead to serious health issues, including effects on the heart and immune system, highlighting the gene's critical role in cellular energy regulation and immune function.