Discovery of anti-appetite molecule released by fiber could help tackle obesity

(Press-News.org) New research has helped unpick a long-standing mystery about how dietary fibre supresses appetite.

In a study led by Imperial College London and the Medical Research Council (MRC), an international team of researchers identified an anti-appetite molecule called acetate that is naturally released when we digest fibre in the gut. Once released, the acetate is transported to the brain where it produces a signal to tell us to stop eating.

The research, published in Nature Communications, confirms the natural benefits of increasing the amount of fibre in our diets to control over-eating and 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.

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 our 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 average diet in Europe today contains about 15 g of fibre per day," said lead author of the study Professor Gary Frost, 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. Unfortunately our digestive system has not yet evolved to deal with this modern diet and this mismatch contributes to the current obesity epidemic. Our research has shown that the release of acetate is central to how fibre supresses our appetite and this could help scientists to tackle overeating."

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. 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 supress appetite."

This is the first demonstration that acetate released from dietary fibre can 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.

Co-author on the study Professor Jimmy Bell from the MRC Clinical Sciences Centre said: "It's exciting that we have started to really understand what lies behind fibre's natural ability to supress our appetite and identified acetate as essential to the process. 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."

Professor Gary Frost added: "The major challenge is to develop an approach that will deliver the amount of acetate needed to supress appetite but in a form that is 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. 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. 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 David Lomas, Chair of the MRC's Population and Systems Medicine Board, added: "It's becoming increasingly clear that the interaction between the gut and the brain plays a key role in controlling how much food we eat. Being able to influence this relationship, for example using acetate to suppress appetite, may in future lead to new, non-surgical treatments for obesity."

INFORMATION: The research was funded by the MRC and the Biotechnology and Biological Sciences Research Council.

For more information please contact:

Franca Davenport
Research Media Officer
Imperial College London
Email: f.davenport@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors

1. Reference: G. Frost et al. 'The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism, Nature Communications (2014), doi: 10.1038/n-comms4611.

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible. 3. The Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk

4. About BBSRC The Biotechnology and Biological Sciences Research Council (BBSRC) invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by Government, and with an annual budget of around £467M (2012-2013), we support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals. For more information about BBSRC, our science and our impact see: http://www.bbsrc.ac.uk For more information about BBSRC strategically funded institutes see: http://www.bbsrc.ac.uk/institutes