Blocked receptor may prevent weight gain

SYDNEY - Drug-based weight loss therapies try to stop the brain from sending hunger signals to the body. These therapies tend to be fairly ineffective. Now researchers have discovered that if certain receptors are blocked in mice, they may be resistant to gaining fat.

The brain normally acts as a master controller, telling us when we are hungry or have eaten enough, instructing one group of cells to burn fat, another to conserve it.

This happens through the neuropeptide Y (NPY) system, neurotransmitters in the brain sending signals to receptors throughout the body.

In the past, neuroscientists have attempted to curtail appetite by blocking NPY signals sent from the brain. Unfortunately, we are so hard-wired to eat that the brain finds ways to evade the blocks, using alternative paths along which to signal.

Herbert Herzog, professor and head of neuroscience program at the Garvan Institute of Medical Research (GIMR), has been studying the infinitely complex NPY system for 17 years, and is well aware how quickly the brain compensates and attempts to change its wiring, or signalling.

For that reason, Herzog and colleagues Lei Zhang and Amanda Sainsbury-Salis decided to leave the brain out of the equation.

They found that if they blocked NPY receptors (Y1) in the peripheral tissues of mice fed with high calorie diets, those mice were resistant to gaining body weight and fat.

(Peripheral tissue is an aggregation of similarly specialised cells which together perform certain special functions).

You fight a losing battle when you try to stop the brain from sending signals, so it makes better sense just to prevent peripheral tissues from receiving them, said Herzog.

We noted that the mice lost fat, rather than muscle, yet continued to eat as normal. There were also no apparent side-effects, Herzog said.

The really advantageous thing about this research is that many drugs are quite difficult to get into the brain, but easy to get into circulation, and so to peripheral tissue.

Researchers see potential for the development either of drugs or antibodies to block Y1 receptors in humans.

Their findings were published online in The International Journal of Obesity.