For the first time, scientists have linked the growth of new brain cells--induced by a compound known as ciliary neurotrophic growth factor (CNTF)--with weight loss in mice. The findings could offer an explanation for why use of the compound in previous studies kept mice at a healthy weight weeks and months after injections of the drug were stopped.
"Normally for any other treatments for obesity that act in the brain, when you stop those drugs, people just completely go back to where they were," says endocrinologist Jeffrey Flier, professor of medicine at Harvard Medical School and the team's leader on the study.
Flier and his team knew from previous studies that the growth factor stimulated an area in the hypothalamus, a part of the brain that plays a role in regulating appetite and a person's energy balance. That same area of the brain is also affected naturally by the hormone leptin, which is produced by fat cells and regulates appetite. So in their new studies, they focused on this area.
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In one experiment, the researchers gave mice that had been on a two-month, high-fat diet a seven-day dose of growth factor and another compound designed to cling to newly divided cells for identification purposes. The mice lost weight and kept it off for two or more weeks. When the scientists examined the hypothalamus, they found that the mice had six times more neuron growth than mice not treated with the drug. And because the new cells responded to doses of leptin, the scientists think that the compound may play a roll in suppressing appetite by triggering the production of leptin.
In another experiment, Flier and his team gave mice the growth factor along with a drug that inhibits cells from dividing. These mice initially lost weight but after they stopped receiving the CNTF, they regained the weight and grew even fatter than the mice that had not been given the compound, but that had been fed a high-calorie diet.
In future studies, Flier hopes to better characterize the new brain cells and investigate whether other factors in the brain may contribute to the growth of the neurons.
