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    Jul 22, 2013

    Gene-disabling mutation linked to severe obesity

    THE mice were eating their usual chow and exercising normally, but they were getting fat anyway.

    The reason: Researchers had removed a gene that acts in the brain and controls how quickly calories are burned. Even though the mice were consuming exactly the same number of calories as leaner mice, they were gaining weight.

    So far, only one person - a severely obese child - has been found to have a disabling mutation in the same gene. But the discovery of the same effect in mice and in the child - a finding published last week in the journal Science - may help explain why some people put on weight easily, while others eat all they want and seem to never gain an ounce.

    It may also offer clues to a puzzle in the field of obesity: Why do studies find that people gain different amounts of weight while overeating by the same amount?

    Scientists have long thought that the reason some people get fat may lie in their genes. They knew body weight was strongly inherited.

    For example, years ago, they found that twins reared apart tended to have similar weights and adoptees tended to have weights like their biological parents, not the ones who reared them. As researchers developed tools to look for the actual genes, they found evidence that many - maybe even hundreds - of genes may be involved, stoking appetites and making people voraciously hungry.

    This rare gene-disabling mutation is intriguing because it seems to explain something different - a propensity to pile on pounds even while eating what should be a normal amount of food.

    Investigators are now searching for other mutations of the same gene in fat people that may have a similar, but less extreme, effect. The hope is that, in the long term, understanding how this gene affects weight gain might lead to treatments for obesity that alter the rate at which calories are burned.

    "The history of obesity for many years has been one of blaming people for lack of self-control," said Dr Joseph Majzoub, chief of endocrinology at Boston Children's Hospital and lead author of the paper.

    "If some of it is due to a slow metabolism, that would completely change the perspective of parents and patients. It really would change the way we think of the disease."