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

When people diet, they often find it virtually impossible to lose weight - the less food they eat, the less energy they burn, and the less weight they lose. Garvan scientists explain the exact brain circuitry behind this phenomenon.
Media Release: 06 February 2013

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 phenomenon is known, scientists at Sydney’s Garvan Institute of Medical Research and the University of NSW have pinpointed the exact brain circuitry behind it and have published their findings in the prestigious international journal Cell Metabolism, now online.

Dr Shu Lin, Dr Yanchuan Shi and Professor Herbert Herzog and his team have been studying the complex processes behind energy balance using various mouse models. They have shown that the neurotransmitter Neuropeptide Y (NPY), known for stimulating appetite, also plays a major role in controlling whether the body burns or conserves energy.

The researchers found that NPY produced in a particular region of the brain – the arcuate nucleus (Arc) of the hypothalamus – inhibits the activation of ‘brown fat’1, one of the primary tissues where the body generates heat.

“This study is the first to identify the neurotransmitters and neural pathways2 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 Professor Herzog. 

“We know that NPY also influences other aspects of the sympathetic nervous system – such as heart rate and gut function – but 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.”

“Evolution has provided us with these mechanisms to help us survive famine, and they are strictly controlled. When people had to survive by finding food or hunting game, they could not afford to run out of energy and die of exhaustion, so their bodies evolved to cope.”

“Until the twentieth century, there were no fast food chains and people did not have ready access to high fat, high sugar, foods. So in evolutionary terms, it was unlikely that people were going to get very fat and mechanisms were only put in place to prevent you losing weight.”

 “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.”

1. Brown fat, or brown adipose tissue, is one of two types of fat, the other being white fat. We are obese when we have too much white fat, which is basically an organ of energy storage. In contrast, brown fat is like a heat generator. Around 50 g of white fat stores 300 kilocalories of energy. The same amount of brown fat burns 300 kilocalories a day.

We are all born with supplies of brown fat around our necks, nature’s way of helping to keep us warm as infants.

Until recently, it was thought that brown fat vanishes in early childhood, but we now know that brown fat is present in all adults.

2. Arcuate NPY communicates directly with tyrosine hydroxylase (TH) neurons in another part of the hypothalamus known as the paraventricular nucleus (PVN). The TH neurons form a kind of relay point, and in turn signal to brown fat cells by activating other neurons in the brain stem.