Wednesday April 30 2014
Human studies are needed to test a potential appetite suppressant
“Pill to switch off hunger possible as 'anti-appetite' molecule discovered,” The Daily Telegraph reports.
The news is based on a study of fermentable carbohydrates (these aren’t easily digested, but can be used by bacteria in the colon of humans and mice).
Researchers fed mice a high-fat diet supplemented with inulin or another carbohydrate called cellulose. Inulin is a carbohydrate found in a number of fibrous foods – when broken down by bacteria in the colon, it produces a molecule called acetate.
They found that mice given the inulin supplement gained less weight and ate less food than mice given a cellulose supplement.
The researchers studied the brains of mice given inulin and acetate, and discovered they affected areas of the brain and processes involved in appetite suppression.
Future research is needed to confirm that the results of this study can be applied to humans. A major issue may be how to help people get an amount of acetate that will suppress their appetite in a safe and acceptable form. This is because diets high in fermentable carbohydrates can cause diarrhoea, bloating, tummy pain and flatulence.
Where did the story come from?
The study was carried out by researchers from Imperial College London, the University of Reading, the Scottish Universities Environmental Research Centre and the Instituto de Investigaciones Biomédicas de Madrid. It was funded by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research and grants from other UK and European organisations.
The study was published in the peer-reviewed journal Nature Communications. This article is open access, so it can be accessed for free from the publisher's website.
The story was covered by The Daily Telegraph, Mail Online and the Daily Express. Coverage was accurate, although all the headlines were overly optimistic.
The Express is wrong to say that an appetite-suppressing pill has been “made”.
What kind of research was this?
This research was carried out on mice.
The researchers had previously demonstrated that feeding mice a diet supplemented with fermentable carbohydrate was associated with:
- reduced energy intake
- body weight
- adiposity (fatness)
- changes in activation patterns in a part of the brain called the hypothalamus, which is known to control food intake
The aim of the latest study was to investigate the effect on appetite control of the most abundant end product of fermentable carbohydrate fermentation in the colon: the short-chain fatty acid acetate.
Animal research is the ideal way to investigate this issue. However, future studies in humans will be required before any “pill that stops you getting hungry” is available.
What did the research involve?
The researchers performed several experiments.
The first experiment examined the effect of fermentable carbohydrates on body weight. Fermentable carbohydrates aren’t easily digested but can be used by bacteria in the colon. Fermentation by bacteria can produce gases, acids and alcohols.
Mice were fed a high-fat diet supplemented with the fermentable carbohydrate inulin (found in wheat, onion, banana, garlic, asparagus and chicory) or the same diet supplemented with cellulose (which forms the cell wall of green plants and is often referred to as “dietary fibre”). Cellulose is poorly fermentable.
The researchers were interested in the effect on appetite control of the most abundant end-product of fermentable carbohydrate fermentation in the colon: short-chain fatty acid acetate. The researchers looked at how acetate is distributed in the bodies of mice. To do this, they radioactively labelled acetate and either introduced it to the blood or the colon. The mice were then imaged using position emission tomography (PET)-scanning to see where the radioactivity ended up.
They then examined if acetate itself could reduce food intake. To do this, mice were injected with acetate or saline (salty water, used as a control), with food intake monitored.
The researchers wanted to see if acetate was changing the pattern of neurons that are activated in a part of the brain called the hypothalamus.
Mice were injected with acetate or saline, and then their brains were scanned.
The researchers also looked at levels of neuropeptides (small protein molecules used by neurons to communicate with each other) and the levels of certain enzymes involved in metabolism.
Finally, the researchers looked at metabolism in the hypothalamus and the whole of the brain. They either fed the mice labelled inulin or injected then with labelled acetate. In this experiment, the researchers labelled inulin and acetate with different isotopes of carbon and examined whether isotopes were found in other molecules in the brain.
What were the basic results?
Mice fed a high-fat diet supplemented with the fermentable carbohydrate inulin gained significantly less weight and ate significantly less food than mice fed a high-fat diet supplemented with cellulose. Mice fed the diet supplemented with inulin had increased levels of short-chain fatty acids, especially acetate, in the colon.
Using radioactively-labelled acetate, the researchers could see that acetate was taken up by the liver and heart, but that approximately 3% ended up in the brain.
After being injected with acetate, mice ate less food in the short term (one and two hours after being injected) than mice injected with saline.
Compared with saline injection, acetate injection increased activation in a part of the hypothalamus called the arcuate nucleus. There were also changes in production of neuropeptides (small protein molecules used by neurons to communicate with each other) to those that favour appetite suppression after acetate injection. They also found that acetate injection changed the levels of activated metabolic enzymes.
After the mice were fed labelled inulin or injected with labelled acetate, the labelled carbon was found in a number of compounds in the whole brain, but predominantly in the hypothalamus. Labelled carbon was found in brain signalling molecules.
How did the researchers interpret the results?
The researchers said they have provided “a novel insight into a mechanism through which [fermentable carbohydrate] may mediate appetite suppression. By exploring the role of short-chain fatty acid acetate, a product of fermentation of carbohydrate in the colon, our evidence suggests that acetate derived from the colon induces an anorectic signal [a signal that suppresses appetite]”.
They go on to say that these findings “open up important new possibilities for weight management as the supply of fermentable substrate to the colon (and therefore acetate production) can be modified”.
This study found that mice fed a high-fat diet supplemented with inulin gained significantly less weight and ate significantly less food than mice fed a high-fat diet supplemented with cellulose.
Additional experiments with inulin and the major product of fermentation of inulin in the gut (acetate) found that they affect the activation of certain regions of the brain, the production of brain signalling molecules and the activity of certain enzymes.
These findings give us some insight into how fermentable carbohydrate may suppress appetite.
Previous research also suggests there are numerous benefits of fermentable carbohydrates. However, people don’t often stick to these diets, as they don’t like the foods that contain high levels of it or because of gastrointestinal side-effects.
One of the researchers stated that a “major challenge is to develop an approach that will deliver the amount of acetate needed to suppress appetite, but in a form that is acceptable and safe for humans”.
Until then, if you are having problems struggling with your appetite, foods that contain fermentable carbohydrates, such as banana and asparagus, may help.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.