ARTICLE
Auteur(s) : Anne Le Guillou1
1Vice-Presidente of AFECG
2DANONE RESEARCH, Centre de Recherche Daniel Carasso
First of all, I would like to emphasize the quality and the
richness of all the presentations. We had the chance at this joint
DGF/AFECG meeting, to have experts from different and complementary
domains & labs.I’m not at all a brain specialist or a
physiologist, nor am I a nutritionist. My job is to select good
sources of fats & oils and to find technical & chemical
parameters for their uses in Danone Biscuits & Dairy Products.
So I learnt a lot during these 2 days! I will try to sum up the
main issues; please forgive me in advance if I missed some points.
PUFA metabolism
We directly entered the key role of PUFA with Pr Crawford who
highlighted the unique importance of DHA in the evolution of
species, and in the evolution of brain. In his view, it seems that
Nature has selected DHA instead of DPA because of one extra double
bond, which allows the molecule to better interact with proteins in
cell membranes. DHA provides brain cells with a unique fluidity. So
what could seem a detail conditions the structure and the activity
of our brain.
We can draw a link with Pr Cunnane’s book, Survival of the
Fattest in which he proposed that seafood DHA boosted the brain
power of early humans, so the fattest could became the fittest.
The production of DHA in our body appears limited, even if we
have in our diet a sufficient amount of precursors like ALA. So,
the knowledge of the various metabolism stages of PUFA in the
nervous cells is essential.
Drs Guesnet and Alessandri presented data on cultured cells; it
seems that there is no limit for DHA incorporation, but limits for
producing DHA from ALA, EPA or DPA are probably due to the
peroxisomal desaturation step.
PUFA for brain development in early life
In the presentations from Drs Demmelmair and Pawlosky, we saw the
importance of Omega 3 and Omega 6 intake during pregnancy and
post-natal period, with impact on short term & long term brain
development; even if the newborn has the capacity to synthesize DHA
from ALA, and ARA from LA.
DHA & ARA are both crucial for the optimal development of
the brain and the eyes.
Dr Demmelmair showed data suggesting a preferential transfer of
DHA from blood to placenta, with the help of Fatty Acid Transer
Protein 4. In the placenta DHA is present mainly in the form of
phospholipids.
Dr Pawlosky proposed an interesting compartimental model for
Omega 6 pathways in newborns, showing turnover, intake and
synthesis.
At the cellular level, Dr Vancassel and Dr Benjamin Buaud,
reported animal studies with diet modifications (deficient or not
in ALA). Dr Vancassel explained that a DHA deficit in neuronal
membranes has an impact on neurotransmission. B. Buaud showed us
that modifications in nuclear receptor expression due to Omega 3
deficiency, would lead to modifications of synaptic plasticity. In
fine, this could induce some behaviour modifications.
PUFA and aging disorders
Alzheimer’s disease has been studied for over one hundred years but
its prevalence continues to increase like our lifespan in
industrialized countries. Once again, DHA plays a specific and key
role in the appearance and evolution of the disease.
Pr Cunnane referred to the recent work of Pr Guesnet on DHA in
brain glucose transport, and highlighted the fact that the brain
has a specific metabolism, particularly for ketone use when glucose
availability is low. Brain DHA level seems to be an important
regulator of brain glucose uptake, particularly for the elderly.
It’s also of importance to understand the role of insulin in brain
glucose metabolism.
Pr Hartmann reviewed the complicated regulation between gamma
secretase/Amyloid Precursor Protein/Amyloid beta, and the link with
lipid homeostasis. It is noteworthy that Amyloid β is involved
in sterol and sphingolipid metabolism. This could lead to new
approaches for the prevention and treatment of Alzheimer Disease
(’AD). A high level of DHA in the diet reduces the formation of
amyloid plaques.
In the same direction, Thierry Pillot reported the
neuroprotective effect of DHA enrichment and fish consumption in
Alzheimer Disease development. Dr Bryhn presented the results of
the first intervention study showing evidence for the positive
effect of supplementation with concentrated fish oil rich in DHA on
the reduction of memory decline at early stages of AD.
Dr Heurtaux focused on alphalinolenic acid (ALA) impact
highlighting the molecular mechanism of neuronal protection induced
by ALA via the activation of a specific potassium channel, the 2
pore domain channel TREK1. In an animal model, ALA activated TREK1,
and reduced induced ischemia & epilepsy. It can also play a
cerebral preconditioning role.
Finally, yesterday Dr Acar discussed the impact and mechanisms
of omega 3 in the retina which contains the highest concentration
on this fatty acid. The eye reflects the importance of getting the
right kind of fat and DHA with positive impact on retinal
diseases.
PUFA role in behaviour troubles and related pathologies
We began with Dr Barberger-Gateau’s presentation on epidemiological
data, which suggested a combined protective effect of long chain
Omega 3 and anti-oxidants against cognitive decline & dementia.
She reported also a significant protective effect from the
consumption of oil rich in omega 3 (rapeseed and nuts) and a
deleterious effect caused by an excess of Omega 6. This was a good
link between yesterday’s presentations on AD, and the following
topics on pathologies.
Dr Astrog reviewed the data available regarding the link between
Omega 3 intake or status and mood disorders like depression. It
seems that a moderate supplementation with EPA combined with an
anti depressor treatment is more effective than a DHA
supplementation.
With Dr Vamecq, we had a cellular level view of the impact of a
ketogenic diet (used for epileptic patients) on astrocyte/neuron
interactions. It emphasizes again the specific metabolism in the
brain, especially under unusual feeding conditions.
Dr Pages’ presentation on Omega 3 from rapeseed oil showed the
results of an animal study with magnesium deficient mice (epilepsy
model), revealing that a chronic diet rich in ALA has a protective
effect on neuronal disorders such as epilepsy. As already
mentioned, interactions between fatty acids and proteins are key in
the understanding of brain health and disease. Pr Spener shared a
review on current knowledge on fatty acids binding proteins (FABPs)
in the brain. The possible use of these molecules as diagnostic
markers was highlighted. FABPs allow DHA to move into the cell.
Without this help, DHA will stay in the membrane.
Then we were pleased to listen to the Medaille Chevreul lecture
by Dr Stanley Rapoport, who showed how DHA is provided to our
brain, with the help of the liver, even when dietary conditions are
difficult (omega3 deficient diet: no intake of ALA). The brain is
an organ totally dependent on DHA, as it does not possess
desaturases. We also saw amazing images of human brain obtained by
positron emission tomography showing AA & DHA consumption.
Perspectives
The bioavability of LCPUFA present in our diet will determine their
level in our brain. Pr Parmentier insisted on the interest of
having PUFA in phospholipids form, especially in sn2 position. Then
he presented an original patented ingredient extracted from salmon
brain, the Phospho-Lipo-Proteic-Complex. So we can claim “directly
from salmon brain to the human brain”…
As we all require DHA in our diet, and as the world population
is still growing, we can wonder whether the marine sources of DHA
would be sufficient to meet human needs. In his talk, Dr Abadi
highlighted the possibility for PUFA production by transgenic
plants.
Pr Lagarde re-emphasized the role of phospholipids and of DHA as
the precursor of neuroprotectin D1, which has potent
anti-inflammatory and cell-protecting properties.
Conclusion
One could have called this congress “Omega 3 & brain”, or even
“DHA & brain” because evidence relates this fatty acid to our
individual development and that of our species. PUFA are key for
the construction of the cerebral structures during pregnancy and
for their maintenance as we age. We now have more than hope for the
prevention and treatment of Alzheimer disease, through the
understanding of the molecular & cellular basis of the disease,
and the role of PUFA.
During these 2 days, we shifted several times from human to
animal and cellular levels. PUFA and especially DHA are key for
membrane fluidity, and for exchanges between the cell and its
environment. Consequently they are key in exchanges between human
beings. Because DHA is difficult to synthesize in our body, even
with good precursor quantity & quality, our brain has set up
strategies of economy and recovery of DHA.
But we should not forget the complementary roles of other PUFA,
and the importance of the ratio between Omega 3 and Omega 6. We
also saw the importance of protein in PUFA metabolism.
Our diet affects the chemistry of our brain, and could influence
our mood and behaviour. Something as simple as eating fish several
times a week, and using rapeseed or flaxseed oils, could help our
brain functions and our social life. The bio availability of PUFA
is also of interest.
Thanks again for your participation, and I hope that we all get
“fat enough” to survive! Take care of your DHA!
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