Rare FNIP1 gene mutation boosts metabolism, cuts cardiometabolic disease risk

Researchers identified a scarce FNIP1 loss-of-function mutation that makes carriers burn calories more efficiently and lowers their odds of obesity, diabetes and related illnesses.

A multinational genetic analysis of more than a million participants highlighted a rare FNIP1 mutation present in roughly one in 7,000 individuals. About 150 people with this loss-of-function variant displayed healthier lipid profiles, reduced liver fat, lower glucose levels, greater muscle proportion and an estimated 60 % reduction in cardiometabolic disease risk. Experiments in cultured liver cells demonstrated that turning off FNIP1 triggers genes that increase fat oxidation, and mice engineered to lack the gene in the liver avoided weight gain, improved insulin sensitivity, and were protected from diet-induced liver damage over 30 weeks.

The research, authored by scientists at Regeneron Pharmaceuticals and published in Nature, argues that the mutation’s effects could guide the development of drugs that mimic its metabolic benefits. However, the authors caution that total systemic inhibition of FNIP1 might cause heart disease and immune problems, especially in individuals with two defective copies, and that any therapeutic approach would likely need to target the liver specifically and remain years away from clinical use.