Courtesy of Kenneth Longo/ University of Michigan Medical School
Fat deposits surround the kidneys of a
normal mouse (left). Mice engineered to overproduce the protein Wnt10b have drastically smaller fat deposits (right) and are leaner; unfortunately, they lack the body fat needed to keep warm.
Biologists investigating pathways associated with obesity have created a genetically modified mouse that can binge on fatty food without gaining weight. The critter’s secret weapon is an overactive version of the gene for a protein—Wnt10b—that regulates the formation of flab. “Wnt10b is a switch that determines whether a pre-fat cell turns into a fat cell,” says Ormond MacDougald, a physiologist at the University of Michigan Medical School, who led the study. “If the switch is turned on, it prevents the development of new fat tissue.”
The modified mice had half as much body fat as normal, even when fed a high-fat diet. In addition, the mutants are less prone to type 2 diabetes because they are more insulin sensitive and more tolerant to glucose. But the trade-offs are scary: MacDougald’s low-fat mice have freakishly thick skin, abridged mammary development, and are hypersensitive to cold. Not surprisingly, MacDougald expects that a gene-targeted treatment for our tubbiness is a long way off.
Nevertheless, the genetic basis for human obesity is becoming increasingly clear. A recent study in Ireland, for example, has uncovered evidence that famine survivors preferentially pass on a gene that helps the body store fat. Back when food was scarce, fat storage was a good way to stay alive. In modern times, those same genes are a prescription for plumpness.