Genetically altered 'skinny' mice could lead to drug to treat obesity

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    Genetically altered 'skinny' mice could lead to drug to treat obesity


    Genetically altered 'skinny' mice could lead to drug to treat obesity: study

    Canadian Press

    Tuesday, November 8, 2005

    TORONTO (CP) - In a discovery with implications for fighting obesity in humans, Canadian scientists have discovered a molecular switch in specially bred laboratory mice that makes the animals skinnier than their normal brethren.
    The altered mice, which lack a certain gene, have half as much fat as normal mice - and the fat they do have isn't the kind that piles on the weight, say researchers at the Ottawa Health Research Institute.
    Anthony Scime, a molecular biologist at the University of Ottawa institute, said the leaner mice have a higher proportion of what are known as brown fat cells, which burn up fat and release it as heat.
    Normal mice - and humans and other mammals, for that matter - have mostly white fat cells, which metabolize fat as energy to fuel muscles and other bodily functions.
    So when food intake exceeds energy output, these white fat cells multiply and expand in girth, Scime said Tuesday from Ottawa. "You just keep on getting bigger and bigger."
    The knocked-out gene in the mice - called P107 - seems to act as a switch on precursor cells, causing them to develop into heat-producing brown fat cells instead of lipid-storing white fat cells, said lead investigator Michael Rudnicki, director of molecular medicine at the institute.
    "The P107 knockout mice eat just as much as normal mice, but they burn off all the extra calories (as heat)," Rudnicki said.
    The discovery could have big implications for treating human obesity, a ballooning public health risk in Canada, where more than five million people are considered obese and many more are overweight. A growing proportion of the country's children also are overweight or obese, setting the stage for cardiovascular disease, diabetes and some cancers later in life.
    "What it's done is open up a new pathway or new way of looking at how the precursor (cell) that decides to make white or brown fat switches on one way or the other," said Scime. "Especially in light of P107 seeming not to have any other deleterious effect on the mice, perhaps in humans, P107 would be a good target for obesity therapy."
    That could mean designing a drug that in effect flips the P107 switch, although Scime predicts such a medication could take 10 to 20 years to come to market.
    "Drugs that inhibit P107 might be able to prevent the body from making white fat," he said. "This could be a particularly effective strategy because previous studies have shown that once white fat cells are created, they are very difficult to get rid of.
    "Also, once brown fat is created, it would continue to burn extra calories off as heat."
    As newborns, about five per cent of our body weight is made up of heat-producing brown fat cells - nature's way of keeping little bodies warm after they leave the womb. But as we age, the proportion of brown fat cells drops dramatically, giving way to more white fat cells.
    "The sole purpose is to keep the body warm," said Rudnicki. "So this brown fat is typically located between the shoulder blades, wrapped around our internal organs close to the heart, and babies have lots of it. People who live outdoors, the homeless or Inuit, have a lot more of it and those people burn a lot of fat to keep warm."
    But compared to humans, most other mammal species are loaded with brown fat cells. It's these cells that allow bears, for instance, to hibernate over the winter, producing enough heat to maintain internal body temperature at a level to keep the bear alive until spring.
    Scime said the P107 knockout mice were originally bred about six years ago so scientists could investigate how certain cells differentiate into muscles. But when no anomalies were found in the muscles of the mice, they "were kind of shelved, put on the back burner," he said.
    But during other experiments using the genetically flawed mice a few years ago, Scime noticed that they were skinnier than their normal counterparts and began trying to find out why.
    "And our study showed that they had a lot of fat precursors (cells) that were not differentiating into fat, and this is why they were lean."
    A paper on the discovery is published in the November issue of Cell Metabolism.

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    Yeah but wouldn't people who stuff themselves and overheat sweat like pigs the hwole time with all the heat being produced by the brown fat?

    Maybe that will be a good method of stopping people from overeating otherwise their clothes get drenched.

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