Scientists Create Mice Resistant to Obesity

By Jeffrey Perkel
HealthDay Reporter
Sunday, August 10, 2008; 3:00 PM

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SUNDAY, Aug. 10 (HealthDay News) -- Researchers have developed a strain of mice resistant to diet-induced obesity.

The findings could one day lead to possible drug treatments for obesity in people. They also shed light on the brain circuitry that controls energy homeostasis -- the balance between how much energy (i.e., food) an animal takes in and how quickly it burns that energy.

Dr. Julio Licinio, a professor of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine, called the research a "technological tour de force."

Dr. Bradford Lowell, associate professor of medicine at Harvard Medical School, led the study, which was published online Aug. 10 in the journal Nature Neuroscience.

According to lead study author Qingchun Tong, most research into energy homeostasis has involved what scientists call genetically encoded neuropeptides, rather than small molecule neurotransmitters.

Neurotransmitters "have been postulated to play a very important role in neurocommunication, but in this field, essentially no critical studies have been performed to address this issue," Tong said. "So I set up an experiment to create an animal model in which a particular group of neurons in the brain couldn't release a small neurotransmitter, and by examining those animal models, I could know the function of those molecules."

Tong and Lowell focused on one neurotrasmitter in particular, called GABA (gamma-aminobutyric acid). They developed transgenic, or mutant, mice that lacked the ability to release GABA in a subset of brain cells in the hypothalamus -- the brain region that controls processes such as hunger, thirst and body temperature.

On a normal diet, the normal and mutant mice weighed roughly the same, with mutant mice weighing slightly less. On a high fat diet, however, the mutant mice gained far less weight than the normal mice, even though the two groups ate approximately the same amount of food. The reason: The mutant mice were burning energy at a faster rate, the researchers said.