The Nerve Cells that Control Obesity

11 April 2017

Interview with

Dr Goncarlo Bernardes, University of Cambridge

The human population is growing, and not just in terms of numbers. The World Health Organisation estimate that nearly half of all adults are now overweight. So the discovery this week of a network of nerve fibres that seem to control when fat cells store energy and get fat is potentially huge news. Biochemist Goncalo Bernardes, who's based at Cambridge University, has engineered a toxin to remove these nerve cells.  Mice given the toxin all became grossly obese, despite eating a normal diet, and this suggests that manipulating these fat nerves might be a way to control weight as he explained to Chris Smith...

Goncalo - We first observed that nerve cells are also present in the fat tissue and this led to the question what happens if we can remove these nerve cells from the fat tissue , how would that influence obesity?

Chris - Right, but how can you remove nerve cells just from fat? Because nerve cells are present in the skin, and they’re also present in the brain, they’re everywhere, so how can you be selective?

Goncalo - To do so, what we have done is to engineer at toxin in such a way that this toxin would not cross the blood/brain barrier and therefore would spare the nerve cells in the brain and selectively influence the nerve cells present in the fat tissue.

Chris - And this is in mice?

Goncalo - And this is in mice.

Chris - So these are otherwise healthy mice and you’ve got a toxin now which selects for the nerve cells which are in the fat cells, so you can remove those nerve cells and see how the fat in the animal changes?

Goncalo - Exactly. Independently of the food intake of these animals. So we gave our engineered toxin to a group of animals and we followed all these mice that got fat or not. So what we have observed in the case of the engineered toxin is that the removal of the neurons from the fat tissue led to very obese mice independently of the amount of food intake.

Chris - So compared to normal animals eating the same diet, these mice that now lacked the nerve cells in their fat tissue gained prodigious amounts of weight?

Goncalo - Yes, that was exactly what we found, without having any brain damage.

Chris - Do you understand why the mice had this preponderance to gain weight?

Goncalo - So this study really points towards the reaction that there is a crosstalk between the nerve cells in the fat tissue and how this is related to obesity. We don’t know all the mechanistic aspects behind it, but that’s something we consider very exciting for sure.

Chris - Do you think this could lead us to a clue as to how we can help people or animals not to become obese?

Goncalo - We are using these findings to do exactly the reverse, and the reverse would be how we can stimulate nerve cells in the fat so that these mice, independently of their food intake, would not get obese.

Chris - Are they relatively easy to stimulate, these nerves? Is there a drug that you could administer that mimics the signals from the nerve cells into the fat cells to make this happen?

Goncalo - Yes. There are drugs that are being used that can stimulate nerve cells and these are the drugs that we are currently designing in a way that they can specifically stimulate the nerve cells in the fat, whilst sparing the nerve cells in the brain.

Chris - Do you think that in humans the same thing might be happening, or at least there might be a contribution from the nervous system leading to people gaining too much weight?

Goncalo - I think you phrase it very well in a way that when we go from smaller organisms to higher organisms such as humans, there is always a certain degree of complexity that is involved. What we are convinced is that there is a contribution from the nerve cells present in fat we can use to try to modulate in humans.

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