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Brain’s appetite circuits could be 'rewired'

“Appetite control could be rewired, say researchers”, BBC News reports, based on findings that it notes “could eventually offer a permanent solution for tackling obesity”.

The news comes from complex cellular research looking at a part of the brain called the hypothalamus, which helps regulate appetite.

This research confirms suggestions that the nerve cells in the hypothalamus are not ‘fixed’ from birth, but can be generated later. Researchers identified a type of cell known as ‘Fgf10-expressing tanycytes’ that could add new nerve cells to the hypothalamus after birth in mice.

This provides clues as to how this part of the brain could be adapted. The researchers suggest that this knowledge could eventually be used to develop novel treatments for obesity and other eating disorders.

However, these experiments were performed in mice, and the researchers did not investigate whether they could control the generation of new nerve cells to control the appetite of obese mice. For these reasons, any chance of ‘rewiring’ human appetite – as the researchers point out – is an incredibly long way off.

Where did the story come from?

The study was carried out by researchers from the University of East Anglia, UK; the University of Helsinki, Finland; University Justus Liebig, Germany; and the University of Los Angeles, US. It was funded by the Wellcome Trust.

The study was published in the peer-reviewed Journal of Neuroscience.

The story was covered by the BBC News, the Daily Express and the Mail Online. BBC News strikes an appropriate note of caution in its coverage and includes a quote from one of the researchers pointing out that this is just a single first step towards a possible, and by no means certain, treatment for obesity in humans.

The coverage in the Mail Online and the Express is a bit more excitable; with claims in their headlines that an ‘obesity pill’ may be available ‘within years’.

Although this research suggests the appetite and energy-balance regulating centres in the brain are not fixed at birth and could possibly adapt, a safe and effective ‘obesity pill’ in humans is still the stuff of science fiction, at least until further research is carried out. The genes and processes involved in this cell addition, and how they could be modified, need to be investigated first.

What kind of research was this?

This was animal-based research studying a type of cell found in the brain, called Fgf10-expressing tanycytes (Fgf stands for fibroblast growth factor-10).

The researchers wanted to see if Fgf10- expressing tanycytes could act in the same way as stem cells or progenitor cells in the production of new cells. They specifically wanted to see if they could stimulate formation of nerve cells (neurons) in a part of the brain called the hypothalamus, after birth. The hypothalamus regulates sleep cycles, appetite, thirst and other critical biological functions.

Some areas of the brain can change and adapt over the course of a lifetime (this is known as plasticity) while others remain relatively unchanged. Until recently it was thought that the majority of the nerve cells in hypothalamus were generated during the embryonic period. However, there is increasing evidence, that this study adds to, that new nerve cell formation occurs after birth and into adulthood.

Animal studies are ideal for investigating this type of question. However, further experimental studies will have to be performed in mice to find out which genes and processes are involved and whether these can be modified.

While it is likely that similar processes to those observed in mice occur in humans, this also needs to be confirmed. The ability to ‘rewire’ the human appetite seems a long way off.

What did the research involve?

The researchers looked at what happened to Fgf10- expressing tanycytes and their ‘daughter’ cells (new cells produced from Fgf10- expressing tanycytes) in the brains of mice.

What were the basic results?

The researchers found that Fgf10- expressing tanycytes resemble neuron stem cells and can divide and generate neurons and glial cells (cells that support and protect neurons).

The researchers found that Fgf10- expressing tanycytes continually add new neurons to the parts of the hypothalamus that regulate appetite and energy balance. Some of these cells expressed a signalling molecule involved in the regulation of appetite.

Some cells responded to fasting, as well as responding to signals from the hormone leptin, which inhibits appetite.

How did the researchers interpret the results?

The researchers conclude that this study provides evidence that new neurons grow in the hypothalamus after birth, into adulthood. They also conclude that they identified Fgf10- expressing tanycyte cells as a source of these neurons, and that these cells have a possible role in appetite and energy balance.

Conclusion

In this study, researchers identified a type of cell that – in mice – can add new nerve cells to the hypothalamus after birth. The new neurons were created in parts of the hypothalamus with a role in regulating appetite, energy balance and feeling full.

Some cells also expressed a signalling molecule involved in the regulation of appetite, and that some cells responded to fasting and signals from the hormone leptin (which inhibits appetite).

Until recently, it was thought all the nerve cells in the brain associated with appetite regulation were produced during the embryonic stage of development so the circuitry controlling appetite was believed to be ‘fixed’.

However, this new research adds to increasing evidence that new nerve cell formation occurs after birth, and into adulthood in the hypothalamus of mammals. Adding new cells could mean there may be ways to adapt appetite, energy balance and satiety, and if these processes could be modified, may lead to treatments for obesity and other eating disorders.

There are, however, a couple of points worth noting; firstly, the researchers did not investigate whether the creation of these additional cells actually had any effect on the appetite or weight of overweight or obese mice. It will also need to be determined if, and how, the process of cell generation in the hypothalamus could be modified. Secondly, and probably more importantly, results of animal studies do not necessarily ‘translate’ over into humans.

Further experimental studies will have to be performed in mice before any studies in humans could be considered. The ability to ‘rewire’ human appetite seems a long way off.  

 

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