Mice that ate the equivalent of two Big Macs and a supersized soda every day lost about 16% of their body weight in two weeks.© Punchstock

An injection that stimulates the growth of new brain cells can cause mice to lose more than 15% of their body weight, researchers say. Experts hope that the treatment, which lasts for weeks, could eventually be made into weight-loss drugs for humans.

The discovery was inspired by the unexpected side effects of a drug that was tested in the 1990s as a treatment for amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease. The drug, called Axokine, did not improve muscle control as much as expected, but trial participants did report a loss of appetite.

Biologists wondered whether this appetite-suppression effect could be harnessed to fight obesity. "People tried to turn lemons into lemonade and ask what such drugs could do for weight control," explains Jeffrey Flier of the Harvard Medical School in Boston, Massachusetts.

The effect with Axokine itself did not yield particularly promising results. Axokine's maker, Regeneron, conducted clinical trials for the drug against obesity in 2003, and then abandoned the idea. But researchers realized that similar drugs might re-wire the brain's desire for food.

Supersized surprise

To investigate the effect further, Flier and his colleagues looked at a compound called ciliary neurotrophic factor (CNTF) that, like Axokine, stimulates nerve cells to grow. They injected tiny amounts of the compound into the brains of mice, targeting a region called the hypothalamus, which is known to influence appetite. They also injected a chemical called BrdU, which tags newly formed cells with a green colour.

The researchers then put the mice on a high-fat, high-sugar diet, equivalent to a human eating two Big Macs and a supersized soda every day. Mice given the CNTF injections lost about 16% of their body weight in the first two weeks and kept the weight off for the full five weeks of the experiment.

Flier's team dissected the animals' brains to find out how the effect occurs. Mice injected with CNTF had roughly five times as many BrdU-tagged brain cells in their hypothalamus than non-injected mice, showing that the treatment stimulates new cell growth. The researchers report their findings in the journal Science¹.

Leptin link

It is not yet clear how the production of new cells in the hypothalamus suppresses the feeding urge. But experts speculate that the extra cells could make the hypothalamus more sensitive to a hormone called leptin, which regulates appetite. This link between leptin, brain development and appetite has been demonstrated before, but it was thought to be fixed soon after birth (see 'Appetite may be hard-wired'). Now it seems it can be changed in adulthood.

"Cranking up the brain's response to leptin could be a way to control food uptake," says Richard Simerly, who studies hormonal control of appetite at the Children's Hospital in Los Angeles. But he stresses that using this approach to develop treatments for human obesity will take time. "It will take a lot of work to get there." 

Harvard Medical School, Boston

• References

  1. Kokoeva M. V., Yin H. & Flier J. Science, 310. 679 - 683 (2005). | Article | PubMed | ISI | ChemPort |