Anti-appetite molecule in dietary fibre could help tackle obesity, study

The identification of an anti-appetite molecule called acetate, which is released naturally when fibre is digested in the gut, may be the key to tackling obesity, according to a new study led by the Imperial College London and the Medical Research Council (MRC).
The research, which was published in the journal Nature Communications, found that once released, the acetate is transported to the brain where it produces a signal to tell a person to stop eating. The researchers said the study confirms the natural benefits of increasing the amount of dietary fibre consumed in order to control over-eating, and that the findings could also help develop methods to reduce appetite. The study found that acetate reduces appetite when directly applied into the bloodstream, the colon or the brain.
“The average diet in Europe today contains about 15 g of fibre per day,” said Professor Gary Frost, lead author of the study, from the Department of Medicine at Imperial College London. “In stone-age times we ate about 100g per day but now we favour low-fibre ready-made meals over vegetables, pulses and other sources of fibre,” he said.
“Unfortunately our digestive system has not yet evolved to deal with this modern diet and this mismatch contributes to the current obesity epidemic,” Professor Frost said. “Our research has shown that the release of acetate is central to how fibre suppresses our appetite and this could help scientists to tackle overeating,” he said.
Study method
Dietary fibre is found in most plants and vegetables but tends to be at low levels in processed food. When fibre is digested by bacteria in the colon, it ferments and releases large amounts of acetate as a waste product. The study tracked the pathway of acetate from the colon to the brain and identified some of the mechanisms that enable it to influence appetite.
The study analysed the effects of a form of dietary fibre called inulin which comes from chicory and sugar beets and is also added to cereal bars. Using a mouse model, researchers demonstrated that mice fed on a high fat diet with added inulin ate less and gained less weight than mice fed on a high fat diet with no inulin. Further analysis showed that the mice fed on a diet containing inulin had a high level of acetate in their guts.
Using positron emission tomography (PET) scans, the researchers tracked the acetate through the body from the colon to the liver and the heart and showed that it eventually ended up in the hypothalamus region of the brain, which controls hunger.
In collaboration with Consejo Superior de Investigaciones Científicas (CSIC) in Madrid, the researchers investigated the effects of acetate in the hypothalamus using a cutting-edge scanning technique called High Resolution Magic Angle Spinning (HR-MAS).
“This complements the PET scans and allows us to follow the metabolism of acetate in the hypothalamus,” said Professor Sebastian Cerdán from CSIC. “From this we could clearly see that the acetate accumulates in the hypothalamus after fibre has been digested,” he said.
“The acetate then triggers a series of chemical events in the hypothalamus leading to the firing of pro-opiomelanocortin (POMPC) neurons, which are known to suppress appetite,” Professor Cerdán said.
The researchers said this was the first demonstration that acetate released from dietary fibre could affect the appetite response in the brain. The research also showed that when acetate was injected into the bloodstream, the colon or the brain it reduced the amount of food eaten by mice
“It’s exciting that we have started to really understand what lies behind fibre’s natural ability to suppress our appetite and identified acetate as essential to the process,” said Professor Jimmy Bell, co-author of the study, from the MRC Clinical Sciences Centre. “In the context of the growing rates of obesity in western countries, the findings of the research could inform potential methods to prevent weight gain,” he said.
Challenge to develop delivery approach for treatment
The researchers said the major challenge would be to develop an approach that would deliver the amount of acetate needed to suppress appetite in a form that was acceptable and safe for humans.
“Acetate is only active for a short amount of time in the body so if we focussed on a purely acetate-based product we would need to find a way to drip-feed it and mimic its slow release in the gut,” Professor Gary Frost said. “Another option is to focus on the fibre and manipulate it so that it produces more acetate than normal and less fibre is needed to have the same effect, providing a more palatable and comfortable option than massively increasing the amount of fibre in our diet,” he said.
“Developing these approaches will be difficult but it’s a good challenge to have and we’re looking forward to researching possible ways of using acetate to address health issues around weight gain,” Professor Frost said.
The researchers said it was becoming “increasingly clear” that the interactions in the gut played a key role in controlling the amount of food a person eats, and that being able to influence this relationship may lead to non-surgical treatments for obesity.
The research was funded by the MRC and the Biotechnology and Biological Sciences Research Council.
Other recent discoveries about the benefits of dietary fibre
Meanwhile, Australian Food News reported in April 2014 that a diet high in dietary fibre appeared to play a role in helping survivors of heart attacks live longer. That research found that those who ate the most fibre had a 25 per cent lower chance of dying in the nine years after their heart attack compared with those who ate the least fibre.