An international team of researchers has 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 was led by Imperial College London and the Medical
Research Council (MRC). It 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 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 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."
The paper, The short-chain fatty acid acetate reduces appetite via a central
homeostatic mechanism, is published in Nature
Communications.