Chemical wars against arachidonic acid: Mice making their own Omega-3
Taka
from colitis
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are
the precursors of potent lipid mediators and play an important role in
regulation of inflammation. Generally, n-6 PUFA promote inflammation
whereas n-3 PUFA have antiinflammatory properties, traditionally
attributed to their ability to inhibit the formation of n-6 PUFA-
derived proinflammatory eicosanoids. Newly discovered resolvins and
protectins are potent antiinflammatory lipid mediators derived
directly from n-3 PUFA with distinct pathways of action. However, the
role of the n-3 PUFA tissue status in the formation of these
antiinflammatory mediators has not been addressed. Here we show that
an increased n-3 PUFA tissue status in transgenic mice that
endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant
formation of antiinflammatory resolvins and effective reduction in
inflammation and tissue injury in colitis. The endogenous increase in
n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid
mediators such as leukotriene B4 and prostaglandin E2. The observed
inflammation protection might result from decreased NF-κB activity and
expression of TNFα, inducible NO synthase, and IL-1β, with enhanced
mucoprotection probably because of the higher expression of trefoil
factor 3, Toll-interacting protein, and zonula occludens-1. These
results thus establish the fat-1 transgenic mouse as a new
experimental model for the study of n-3 PUFA-derived lipid mediators.
They add insight into the molecular mechanisms of inflammation
protection afforded by n-3 PUFA through formation of resolvins and
protectins other than inhibition of n-6 PUFA-derived eicosanoid
formation.
SOURCE: http://www.pnas.org/content/103/30/11276.full
doi: 10.1073/pnas.0601280103
John Hasenkam
genetic strain also has increased susceptibility to retinal degeneration and
that 4HHE, the oxidation of DHA, being one of the culprits. I accept those
results because I found other supporting evidence but as a general rule I'm
rather wary of transgene studies.
John.
"Taka" <taka...@gmail.com> wrote in message
news:dd60a0db-cb9f-410b...@p29g2000yqh.googlegroups.com...
Transgenic mice rich in endogenous omega-3 fatty acids are protected
from colitis
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are
the precursors of potent lipid mediators and play an important role in
regulation of inflammation. Generally, n-6 PUFA promote inflammation
whereas n-3 PUFA have antiinflammatory properties, traditionally
attributed to their ability to inhibit the formation of n-6 PUFA-
derived proinflammatory eicosanoids. Newly discovered resolvins and
protectins are potent antiinflammatory lipid mediators derived
directly from n-3 PUFA with distinct pathways of action. However, the
role of the n-3 PUFA tissue status in the formation of these
antiinflammatory mediators has not been addressed. Here we show that
an increased n-3 PUFA tissue status in transgenic mice that
endogenously biosynthesize n-3 PUFA from n-6 PUFA leads to significant
formation of antiinflammatory resolvins and effective reduction in
inflammation and tissue injury in colitis. The endogenous increase in
n-3 PUFA and related products did not decrease n-6 PUFA-derived lipid
mediators such as leukotriene B4 and prostaglandin E2. The observed
inflammation protection might result from decreased NF-�B activity and
expression of TNF�, inducible NO synthase, and IL-1�, with enhanced
Taka
> There you go Taka, just this week I read two articles indicating that this
> genetic strain also has increased susceptibility to retinal degeneration and
> that 4HHE, the oxidation of DHA, being one of the culprits. I accept those
> results because I found other supporting evidence but as a general rule I'm
> rather wary of transgene studies.
According to the popular opinion this mouse should be protected from
Omega-6 overload because it will convert the vegetable oils in the
feed into the fish oil inside its own body. And it should be
therefore immune to all those degenerative disease ... I have been
challenging the Omega-3 advocates and shills here for some time to
bring me a study demonstrating that Omega-3s extend the maximum life
span. Yet they are able to come up only with a single study cited
over and over which says that DHA did not affect lifespan based on
some dubious statistics but admits (in its title!) that "N-3
polyunsaturated fatty acids impair lifespan". Because none of the
modern researchers will do a lifespan study with PUFA/EFA versus SFA
feeding they may look at the eyes as a faster indicator of the lipid
peroxidative stress and relate it to the lifespan. Retinal
degeneration and cataracts are all the signs of aging and Omega-3s
don't save the eyes from them at the best. If removal/substantial
reduction of the Omega-6/AA will keep the eyes healthier longer and
extend the maximum lifespan remains to be seen but my "educated guess"
is that it will. Sometimes the personal experience is better than
hundred meta analysis review articles and I have such experience
because I had been misled by the Omega-3 propaganda for some time.
And don't forget that we have now even transgenic pigs and plants
manufacturing their DHA/EPA as well as yeast making their own "EFAs":
Transgenic Res. 2006 Aug;15(4):405-7.
Cloned transgenic heart-healthy pork?
Prather RS.
Division of Animal Sciences, University of Missouri-Columbia, 920 East
Campus Drive, E125 Animal Science Research centre, Columbia, MO 65211,
USA.
Here I comment on the production and uses of swine that express a
humanized fat-1 gene. The gene product is a fatty acid desaturase that
converts omega-6 fatty acids to omega-3 fatty acids. Omega-3 fatty
acids have been implicated as being important for reproductive
success, maintaining a healthy cardiovascular system, sustaining a
functional immune system, and even preventing depression and cancer.
The descendants of these hfat-1 transgenic swine will be very useful
as models of the human condition, and if they are permitted to enter
the food chain, they may improve human health.
PMID: 16906441, 16565727
Nat Biotechnol. 2004 Jun;22(6):739-45. Epub 2004 May 16.
Production of very long chain polyunsaturated omega-3 and omega-6
fatty acids in plants.
Qi B, Fraser T, Mugford S, Dobson G, Sayanova O, Butler J, Napier JA,
Stobart AK, Lazarus CM.
School of Biological Sciences, University of Bristol, BS8 1UG,
England, UK.
We report the production of two very long chain polyunsaturated fatty
acids, arachidonic acid (AA) and eicosapentaenoic acid (EPA), in
substantial quantities in a higher plant. This was achieved using
genes encoding enzymes participating in the omega3/6 Delta8 -
desaturation biosynthetic pathways for the formation of C20
polyunsaturated fatty acids. Arabidopsis thaliana was transformed
sequentially with genes encoding a Delta9 -specific elongating
activity from Isochrysis galbana, a Delta8 -desaturase from Euglena
gracilis and a Delta5 -desaturase from Mortierella alpina.
Instrumental in the successful reconstitution of these C20
polyunsaturated fatty acid biosynthetic pathways was the I. galbana
C18-Delta9 -elongating activity, which may bypass rate-limiting steps
present in the conventional Delta6 -desaturase/elongase pathways. The
accumulation of EPA and AA in transgenic plants is a breakthrough in
the search for alternative sustainable sources of fish oils.
PMID: 15146198
Free Radic Biol Med. 2006 Mar 1;40(5):897-906. Epub 2005 Nov 8.
Saccharomyces cerevisiae strain expressing a plant fatty acid
desaturase
produces polyunsaturated fatty acids and is susceptible to oxidative
stress induced by lipid peroxidation.
Cipak A, Hasslacher M, Tehlivets O, Collinson EJ, Zivkovic M,
Matijevic
T, Wonisch W, Waeg G, Dawes IW, Zarkovic N, Kohlwein SD.
Institute Rudjer Boskovic, Zagreb, Croatia.
Although oxygen is essential for aerobic organisms, it also forms
potentially harmful reactive oxygen species. For its simplicity, easy
manipulation, and cultivation conditions, yeast is used as an
attractive
model in oxidative stress research. However, lack of polyunsaturated
fatty acids in yeast membranes makes yeast unsuitable for research in
the field of lipid peroxidation. Therefore, we have constructed a
yeast
strain expressing a Delta12 desaturase gene from the tropical rubber
tree, Hevea brasiliensis. This yeast strain expresses the heterologous
desaturase in an active form and, consequently, produces Delta9/
Delta12
polyunsaturated fatty acids under inducing conditions. The functional
expression of the heterologous desaturase did not affect cellular
morphology or growth, indicating no general adverse effect on cellular
physiology. However, the presence of polyunsaturated fatty acids
changed
the yeast's sensitivity to oxidative stress induced by addition of
paraquat, tert-butylhydroperoxide, and hydrogen peroxide. This
difference in sensitivity to the latter was followed by the formation
of
4-hydroxy-2-nonenal, one of the end products of linoleic fatty acid
peroxidation, which is known to play a role in cell growth control and
signaling. Here we show that this yeast strain conditionally
expressing
the Delta12 desaturase gene provides a novel and well-defined
eukaryotic
model in lipid peroxidation research. Its potential to investigate the
molecular basis of responses to oxidative stress, in particular the
involvement of reactive aldehydes derived from fatty acid
peroxidation,
especially 4-hydroxy-2-nonenal, will be addressed.
PMID: 16520241
--------------------
In respect to the DHA-rich retinas I would love to compare the
composition of retina's FAs of the long lived songbirds (birds in
general have the best eyes) with mice or rats. Songbirds/parrots have
been shown to possess more saturated FAs in their membranes because
they need to keep their brains undamaged and functional for longer
time to memorize the complex songs.
Taka
P.S.: Guess what will happen to the cats eating these Omega-3 versus
normal wild mice in the longer term ...
John Hasenkam
The problem with so many studies is that the statistical analyses are often
flawed. A complete pain in the ass, in fact a paper was released last week
with the title< Why most research findings are false.
Yes, I agree there is far too much ranting about omega 3's, walk into any
health food shop. We need some, not a lot, we also need cholesterol at good
levels(there is a huge cholesterol furphy going on out there), saturated
fats to strengthen cell walls, and monos for a whole range of things.
I have a completely different epistemological style for addressing these
issues. I think most meta analyses are a con and most people adopt a
mathematical fundamentalism that is laughable and naive. As Steve Jones, a
geneticist, once quipped: There are two kinds of scientists: those who use
mathematics and those who understand mathematics.
--
http://healthycuriousity.blogspot.com/
"Taka" <taka...@gmail.com> wrote in message
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