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The brain circuit that makes it hard for obese people to lose weight

Feb 15, 2013

Researchers in Australia explain why when obese people diet, they end up losing less weight.
Imagine you are driving a car, and the harder you press on the accelerator, the harder an invisible foot presses on the brake. That’s what happens when obese people diet – the less food they eat, the less energy they burn, and the less weight they lose.
While this is a known phenomenon, scientists at Sydney’s Garvan Institute of Medical Research and the University of New South Wales (UNSW) have pinpointed the exact brain circuitry behind it using various mouse models. 

In the journal Cell Metabolism, Dr. Shu Lin, Dr. Yanchuan Shi, and Professor Herbert Herzog and his team show that the neurotransmitter Neuropeptide Y (NPY), known for stimulating appetite, also plays a major role in controlling whether the body burns or conserves energy.

“This study is the first to identify the neurotransmitters and neural pathways that carry signals generated by NPY in the brain to brown fat cells in the body. It is also the first to show a direct connection between Arc NPY, the sympathetic nervous system and the control of energy expenditure,” said Herzog.
The researchers found that NPY – produced in a particular region of the brain called the arcuate nucleus (Arc) of the hypothalamus – inhibits the activation of ‘brown fat,’ one of the primary tissues where the body generates heat.

While NPY also influences other aspects of the sympathetic nervous system such as heart rate and gut function, its control of heat generation through brown fat seems to be the most critical factor in the control of energy expenditure.

“When you don’t eat, or dramatically curtail your calorie intake, levels of NPY rise sharply. High levels of NPY signal to the body that it is in ‘starvation mode’ and should try to replenish and conserve as much energy as possible. As a result, the body reduces processes that are not absolutely necessary for survival,” he said.

Until the twentieth century, people did not have ready access to foods high in fat and sugar, said Herzog. So in evolutionary terms, the body had mechanisms in place only to prevent weight loss, he said.
“Obesity is a modern epidemic, and the challenge will be to find ways of tricking the body into losing weight – and that will mean somehow circumventing or manipulating this NPY circuit, probably with drugs,” he said.

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