Scientists have discovered a gene that, when mutated, makes mice grow obese without boosting their appetite. The finding, reported in tomorrow's Proceedings of the National Academy of Sciences, surprisingly suggests that white blood cells, key immune fighters, help regulate body fat.
During the past few years, researchers have linked mutations in five different genes to obesity in mice. For instance, a defective version of the gene coding for the hormone leptin results in ravenous mice that can't burn enough fat. Now cell biologists Denisa Wagner, Zhao Ming Dong, and their colleagues at Harvard Medical School in Boston have stumbled onto another obesity gene. The team was studying how white blood cells contribute to atherosclerosis, or hardening of the arteries. But when they studied mice lacking the gene for intercellular adhesion molecule-1 (ICAM-1), which helps white blood cells stick to blood vessels and other tissue, the mice grew obese.
Intrigued, the researchers allowed two groups of mice--normal and ICAM-1 mutants--to eat unlimited amounts of mouse chow. Every 2 weeks, they weighed the mice and measured how much food they had eaten. After 6 months, both male and female mice lacking the ICAM-1 gene weighed about 21% more than the controls--even though they ate the same amount of food. When fed a high-fat diet, however, mutant females were much more susceptible to obesity, tipping the scales at 48% heavier than controls. The sexes also put on the weight unequally. "The females really have big tummies," Wagner says, while "the males are chubbier overall." Although abdominal fat increases the risk of atherosclerosis, the connection to people isn't clear, says Wagner, because it's men who usually develop a spare tire around the gut.
"It's an intriguing and surprising finding," says Jeffery Friedman, a molecular biologist at The Rockefeller University in New York City. For now, though, the mechanism is a mystery. Wagner suspects that one of the many chemical messengers released by white blood cells might influence the efficiency of fat storage or metabolism. For example, by preventing these cells from sticking to fatty tissue, mutations in the ICAM-1 gene could be severing such communications. Wagner now plans to look for the ICAM-1 mutation in obese people.