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Put your feet up to slim down?

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“The key to losing weight could be as simple as putting your feet up,” suggests the Daily Mail.

The newspaper reported that “scientists have found a gene that makes us crave sweet and fatty foods and pile on the pounds when under stress”.

This news story is apparently based on research which found that genetically modified mice were more anxious when scientists switched on a gene that produces a brain chemical called urocortin-3. The study found that the stressed mice metabolised food in a different way to normal mice, with their bodies preferring to burn carbohydrates rather than fats. The study actually found that there was no difference in the amount of food the mice ate, and it did not look at whether, if given a choice, the mice would preferentially choose sweet or fatty foods.

Further study may be warranted to look at the role of urocortin-3 in metabolism in humans. However, it is not clear from this animal study how human urocortin-3 production would be affected by stimuli, or whether elevated urocortin-3 would lead to changes in weight or eating. There is also insufficient evidence to suggest that reducing anxiety levels alone is enough to lose weight.

Where did the story come from?

The study was carried out by researchers from the Weizmann Institute of Science, Rehovot, Israel. It was funded by various Israeli funding foundations and personal sponsors. The study was published in the peer-reviewed medical journal Proceedings of the National Academy of Sciences (PNAS).

This study was not reported accurately by the newspapers. They had wrongly suggested that the gene that produces urocortin-3 increases craving for sweets and comfort food. They also said that scientists had discovered a gene that will trigger comfort eating at times of stress. The study in genetically modified (GM) mice did not look at food preferences of anxious mice. In fact, it found that the amount of food they consumed was not altered.

Additionally, as this was an animal study that used genetically modified animals, its direct relevance to humans is limited without further research. While the study showed that increasing the production of urocortin-3 increased anxiety in mice, it is not clear how the anxiety felt by humans would affect their urocortin-3 levels or if a change in urocortin following stress would have any effect on their weight or risk of diabetes.

What kind of research was this?

The brain releases certain chemicals to control basic body functions, such as the regulation of temperature, hunger, thirst and our sleep-wake cycles. The area of the brain that releases these  chemicals is called the hypothalamus, which plays a major role in linking the nervous system with the endocrine (hormone) system. During times of stress, our brain responds by changing our behaviour and changing how the body regulates the metabolism of food by altering the metabolic rate, appetite and feeding behaviours. The research investigated a chemical produced by the brain in the hypothalamus called urocortin-3. It has been suggested that levels of this chemical increase in response to stress.

This study aimed to further investigate the role that this chemical played in the stress response. This was an animal study in genetically modified mice. In these mice, researchers switched on a gene that produced urocortin-3 in order to look at the effect that producing more of this hormone would have on the animals’ behaviour and metabolism.

What did the research involve?

The researchers made a genetically modified mouse that contained a gene for urocortin-3 by injecting a virus containing the gene into the hypothalamus. The gene could be switched on by giving the mice a chemical called Dox in their drinking water.

The researchers assessed the mice’s anxiety levels using behavioural tests. One test involved placing the mouse in an illuminated box. The researchers measured the amount of time that the mouse spent in the centre of the box, and how much and how fast the mouse moved around the box. An anxious mouse will spend less time in and will slowly approach the centre of the box. Another test used a box with a light compartment and a dark compartment connected by a small passage. They measured the mouse’s anxiety by the number of times the mouse ventured into the light compartment. Anxious mice are more reluctant to venture into the light.

They estimated each mouse’s metabolic activity by monitoring their breathing rate by measuring their oxygen consumption and carbon dioxide production. They recorded how much the mice moved around the cage, the glucose levels in the mice, the mice’s insulin levels, and how their glucose levels responded to an injection of insulin. Finally, they assessed the mice’s fat and muscle mass using MRI.

What were the basic results?

The researchers found that the genetically modified mice showed an increase in anxiety-like behaviour, with mice venturing less often into the centre of an open box or into a lit compartment from a dark compartment. However, the mice moved around as much (in dark areas), which suggests that their ability to move was not affected.

The genetically modified mice that produced more urocortin-3 did not eat more food than control mice, but they found that the metabolism of GM mice burned more carbohydrate rather than fat. They also produced more body heat. However, there was no difference in the amount the mice moved around.

There was no difference in the GM mice’s ability to respond to changes in glucose, but the insulin system of the GM mice was less sensitive than normal mice.

How did the researchers interpret the results?

The researchers suggested that the urocortin-C levels released by a group of neurones in the hypothalamus can mediate both behavioural and metabolic response. They suggest that these responses would collectively promote coping with a stress. They said that their research may pave the way towards a better understanding of the relationship between stress, abnormal responses to stress and metabolism.


This study showed that increasing urocortin-C levels in mice made them more anxious and caused changes to their metabolism of fats and carbohydrates. But it did not affect the mice’s food intake or how much they moved around.

While this study showed that increasing the production of urocortin-3 increased anxiety in mice, it is not clear how the anxiety experienced by humans would affect their urocortin-3 levels or whether a change in urocortin following stress would have any effect on weight or risk of diabetes. There is also insufficient evidence to suggest that reducing anxiety levels alone is enough to lose weight.

In short, this animal study performed early research on genetically modified animals, meaning its direct relevance to humans is limited without further research. As such, news reports on this story seem to be based on speculation and assumption beyond the limited implications of this animal research.

Links to the headlines

High stress levels can make you fat, researchers claim. Daily Mail, May 7 2010

Scientists find anxiety gene that also makes you comfort eat. The Daily Telegraph, May 7 2010

Links to the science

Kuperman Y, Issler O, Regev L et al. Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis. PNAS May 4, 2010 vol. 107


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