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Making Obese Mice Slim, Without Diet or Exercise
Date:6/3/2009

the other study, researchers were able to restore blood glucose levels in obese, severely diabetic mice to normal -- again without changing their diets or activity levels.

The mice in the study lacked leptin and receptors in the brain for leptin, a hormone that is involved with many bodily functions, including regulating appetite and metabolism. As a result, the mice became morbidly obese and diabetic.

When researchers added leptin receptors to a particular type of neuron (pro-opiomelanocortin neurons) in the hypothalamus of the mice's brains, their blood glucose levels dropped to normal.

The mice, which had previously lain around all day, became more active. They also ate 30 percent fewer calories and lost a little weight, though the drop in blood glucose levels was independent of that, the study found.

"This gives us the opportunity to search for drugs that might induce the desire or will to voluntarily exercise," said study author Christian Bjorbaek, an associate professor of medicine at Harvard Medical School.

Figuring out how to use leptin to help humans struggling with obesity has proven elusive.

More than 15 years ago, there was a flurry of excitement when studies in mice showed that giving them leptin caused them to lose their body fat, Bjorbaek said.

But later research found that obese people don't lack sufficient leptin. For reasons not fully understood, their cells are resistant to it.

Researchers hope their study will provide clues about ways to develop drugs to target neurons or other pathways in which leptin plays a key role.

"The hope is there will be new drugs that would target the neurons or the downstream pathways of the neurons to help control blood glucose in people who suffer from type 2 diabetes and who are obese," Bjorbaek said.

Weiss said the study sheds more light on the complex mechanisms controlling weight, blood sugar, appetite and phys
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