Fat under fire. FAT-ATTAC mice injected with a specific chemical shed their fat (right) versus those given a placebo (left).

Fat Under Attack

Staff Writer

Talk about melting away the pounds. Researchers have developed a new mouse that sheds its fat when injected with a certain chemical. The mouse's creators hope the animal will offer insights not only into the biology of fat, but also into diseases driven by obesity and even the genesis of certain cancers.

The fatless mouse, dubbed FAT-ATTAC, isn't the first of its kind. Scientists had generated other genetically modified mice that are fatless from birth. But those animals often have an array of other defects, such as severe insulin resistance, which makes it difficult to isolate the role played by fat--or its absence.

Physiologist Philipp Scherer of the Albert Einstein College of Medicine in New York City, with his colleagues, set out to create animals that developed normally into adulthood and whose fat stores could then be melted away at will. To accomplish this, the team genetically altered the fat cells of mice so that a certain chemical would lock on to a molecule inside fat cells, setting off a chain reaction that compels the cells to commit suicide. FAT-ATTAC mice injected with the chemical lost all their fat within 3 or 4 days, says Scherer. Their appetites also surged, suggesting a link between rapid fat loss and high metabolism (since the mice couldn't store the energy they were consuming), though Scherer isn't sure what's behind that change.

The mice also have far lower levels of inflammatory markers in their blood, the group reports in the 19 June online edition of Nature Medicine. Scherer says that suggests that obesity helps mediate inflammation and adds credence to the idea that obesity-related diseases, such as type 2 diabetes, are partly inflammatory in origin.

Technologically, this mouse "is a first," says Michael Schwartz, an endocrinologist at the University of Washington in Seattle. He thinks it could be used to study how, for example, both obesity and lipodystrophy, a rare condition in which fat atrophies, lead to insulin resistance. Scherer also wonders whether the mice could answer a question that fascinates him: whether and how blood vessel proliferation in fat tissue can power certain cancerous lesions, such as early breast cancers.

Related sites
Philipp Scherer's home page
Information on adult obesity from the National Institutes of Health
Background on lipodystrophy

Posted in Biology