People need to eat, like to eat and are programmed to eat.  Australian neuroscientists took these truths to be self-evident before embarking on a radically new direction in weight loss research.

Current drug-based weight loss therapies try to stop the brain from sending hunger signals to the body. These therapies tend to be fairly ineffective, researchers reasoned, so why not reverse the approach and stop the body from receiving signals from the brain? So that’s what they did, and it worked. In mice at least.

In the control of appetite and energy expenditure, 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.

Professor Herbert Herzog, Head of the Neuroscience Program at the Garvan Institute of Medical Research, 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 Dr Lei Zhang and Dr 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. Their findings are now published online in The International Journal of Obesity.

“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.

“The NPY system also plays quite a large role in the stress response as well as appetite and satiety, so if you start blocking one area, you risk side effects in another.”

“We’ve shown here that if you only interfere with the peripheral receptors, you will receive beneficial effects on the general energy balance of the body without interfering with the appetite side.”

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

“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.

ABOUT GARVAN
The Garvan Institute of Medical Research was founded in 1963.  Initially a research department of St Vincent's Hospital in Sydney, it is now one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff. Garvan's main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan's mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan's discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

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a.heather "at" garvan.org.au