For decades, the mantra for weight loss has been simple: “Eat less, move more.” But what if the real culprit behind stubborn weight gain isn’t your willpower, but written in your DNA? A new study reveals that a rare genetic quirk, found in roughly 1 in 5,000 people, could be silently hijacking metabolism, making it nearly impossible to stay slim no matter how hard you try.
Researchers from the University of Exeter, collaborating with Swedish and Danish scientists, analyzed genetic data from nearly 500,000 people in the UK Biobank. They pinpointed a tiny group with just 104 individuals carrying a mutation that deactivates a protein called SMIM1.
Those with this glitch, known as Vel negative status, faced an uphill battle with weight: women weighed an average of 10 pounds (4.6 kg) more than peers, while men carried an extra 5.3 pounds (2.4 kg).
“This isn’t about laziness or late night snacks,” says lead author Mattia Frontini, associate professor at the University of Exeter Medical School. “For these individuals, obesity is baked into their biology.”
The Metabolism Mystery SolvedSMIM1 was discovered a decade ago as a blood cell antigen, but its role in metabolism shocked scientists. When deactivated, it throws a wrench into the body’s energy burning machinery. Vel negative people burn fewer calories at rest, their metabolic engines stuck in low gear. This “genetic lottery” traps them in a cycle of weight gain, even with normal diets and activity levels.
The implications are massive. With global obesity rates tripling in 50 years—and projected to hit 1 billion cases by 2030—this discovery could rewrite how we tackle the crisis. “For most, obesity stems from lifestyle, environment, and genes,” Frontini explains. “But for a small minority, it’s purely genetic. That’s where targeted therapies could change lives.”
From Blood Labs to Weight Loss ClinicsThe team didn’t stop at genes. They analyzed fresh blood samples from Vel negative and Vel positive donors, confirming SMIM1’s metabolic role. Worldwide, an estimated 300,000 people likely carry this mutation, unknowingly fighting biology to lose weight.
Now, the race is on to turn this insight into action. Researchers aim to develop treatments that compensate for SMIM1’s absence, potentially unlocking weight loss for those genetically “stuck.” Imagine a future where a simple blood test identifies Vel negative individuals, guiding them to personalized therapies instead of generic diet plans.
Obesity costs the global economy trillions annually, driving diseases like diabetes, heart failure, and cancer. Yet current solutions—drugs, surgery, or willpower fail millions. “This isn’t just about vanity,” Frontini stresses. “It’s about preventing suffering and saving healthcare systems from collapse.”
Critics caution that SMIM1 is just one piece of obesity’s complex puzzle. But for Vel negative individuals, it’s a game changer. “Finally, we have proof it’s not their fault,” says one obesity specialist not involved in the study. “Science is giving them answers—and hope.”
As research advances, one truth becomes clear: The era of one size fits all weight loss is over. The future belongs to precision medicine, where genes light the path to solutions. For those born with this hidden metabolic flaw, relief may finally be in sight.