New insight into the catch-22 of obesity and dieting

Australian researchers have unravelled a longstanding mystery of obesity: why is it sometimes counterproductive for obese people to diet?

Any sensible diet advice will tell you not to starve yourself because your body will react by storing as much energy as it can in the form of fat. This mechanism, which evolved to keep us going in times of famine, introduces a vicious cycle for many obese people, making it nearly impossible to eat less and burn more energy at the same time.

Now researchers from Sydney’s Garvan Institute and the University of New South Wales have revealed the neural circuitry underlying this phenomenon, raising the prospect of new ways to break the cycle.

The team of scientists led by Dr Shu Lin, Dr Yanchuan Shi and Professor Herbert Herzog focused on the neurotransmitter neuropeptide Y (NPY) and its role in regulating the body’s energy expenditure.

NPY is already well known as an appetite stimulator. However, amongst other effects, its signalling also has an effect on brown adipose tissue, known as ‘brown fat’.

While white fat is the tissue that stores energy, and thus can make one obese when the storage becomes excessive, brown fat is known to work as a heat generator that burns energy, helping keep the body warm.

Using various mouse models, the researchers were able to determine that NPY produced in the arcuate nucleus (Arc) of the hypothalamus in the brain could control the way the body regulated temperature while maintaining a steady equilibrium of energy use.

It appears to do this by decreasing sympathetic nervous system activity, so when brown fat activation is inhibited and it does not generate as much heat, the body burns fewer calories. Thus the catch-22 of dieting.

According to Professor Herzog, this study is the first to show a direct connection between Arc NPY, the sympathetic nervous system and the control of energy expenditure. With an understanding of this brain circuit in place, researchers are now looking towards tinkering with it to aid weight loss.

“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,” said Herzog.

The study was published today in Cell Metabolism.

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