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Medical Forum / General / Nutrition / June 2008

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Desaturases, metabolic syndrome and other "chronic" inflammatory     conditions

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Taka - 28 Jun 2008 10:25 GMT
What the following papers are trying to suggest is that the activities
of the FA desaturases, particularly the delta5, are related to the
insulin resistance and the like and that their activities are affected
by maternal nutrition or smoking (and trans fat consumption AFAIK).
What they don't tell you, however, is that the same enzymes also work
on the Omega-9 series of fatty acids to produce the Mead acid.  As
long as the "experts" are going to ignore this fact and keep focusing
on the Omega-6+3 PUFAs only there will be no cures to the modern
illnesses and the vegetable oil industries and hospitals will
flourish.

Taka

Diabetologia. 2005 Oct;48(10):1999-2005. Epub 2005 Aug 13.

Fatty acid composition of serum lipids predicts the development of the
metabolic syndrome in men.

AIMS/HYPOTHESIS: Types of dietary fat have been related to components
of the metabolic syndrome. Serum fatty acid composition mainly
reflects dietary fat intake, but also endogenous fatty acid synthesis
catalysed by Delta-desaturases. It is not known whether alterations of
fatty acid composition or desaturase activities predict metabolic
syndrome. MATERIALS AND METHODS: We prospectively evaluated fatty acid
composition in serum cholesteryl esters and estimated desaturase
activities in 1,558 50-year-old men taking part in a population-based
cohort study. The follow-up time was 20 years. Stearoyl-CoA desaturase
(SCD-1), Delta6 (D6D) and Delta5 (D5D) desaturases were estimated as
precursor to fatty acid ratios. RESULTS: High activity of estimated
SCD-1 (odds ratio=1.29, p<0.05) and D6D (odds ratio=1.35, p<0.05), as
well as low estimated D5D activity (odds ratio=0.71, p<0.001)
predicted the development of metabolic syndrome (as defined by the
National Cholesterol Education Program). The predictive value of D5D
activity was independent of lifestyle factors (smoking, BMI and
physical activity), whereas the risk associated with higher SCD-1 and
D6D activities was mainly explained by obesity. Among those developing
metabolic syndrome (119 out of 706) during follow-up, the proportions
of fatty acids 14:0, 16:0, 16:1 (n-7), 18:1 (n-9), 18:3 (n-6) and 20:3
(n-6) were increased at baseline, while 18:2 (n-6) was decreased
(p<0.05 for all). CONCLUSIONS/INTERPRETATION: Serum fatty acid
composition predicts the long-term development of the metabolic
syndrome, and D5D activity may be particularly important in this
process. Our results suggest a role of dietary fat quality in the
development of metabolic syndrome, but the possibility that altered
fatty acid composition, partly secondary to genetic or hormonal
factors, should also be considered. Publication Types: Research
Support, Non-U.S. Gov't

Br J Nutr. 2007 Dec 6;:1-4

Serum fatty acid composition and indices of stearoyl-CoA desaturase
activity are associated with systemic inflammation : longitudinal
analyses in middle-aged men.

Altered fatty acid (FA) composition is related to insulin resistance
and CVD. One possible mediator may be inflammation, but longitudinal
data relating FA composition to inflammation taking insulin resistance
into account are limited. We investigated the long-term association
between FA composition and C-reactive protein (CRP) concentrations in
a large population-based cohort study in 767 men followed for 20
years. The association between FA composition in serum cholesteryl
esters at age 50 and CRP concentrations at age 70 was investigated
using linear regression. In addition, desaturase activities (stearoyl-
CoA desaturase-1 (SCD-1), Delta5- and Delta6-desaturase) were
estimated using FA product-to-precursor ratios. Insulin resistance was
measured directly at follow-up by euglycaemic clamp. After adjusting
for confounders (smoking, physical activity, alcohol intake, obesity
and erythrocyte sedimentation rate) CRP concentrations were inversely
associated with the proportion of 18 : 2n-6 (P = 0.002) and positively
associated with 16 : 1n-7 (P = 0.008), 18 : 1n-9 (P = 0.0003), 20 :
5n-3 (P = 0.04) and estimated SCD-1 (P = 0.005) and Delta6-desaturase
(P = 0.02) activities. After adding insulin resistance to the model,
18 : 1n-9, 18 : 2n-6 and SCD-1 remained significant predictors of CRP.
A FA composition indicating low intake of 18 : 2n-6, high intake of
SFA and high SCD-1 activity is, in a Swedish population of middle-aged
men, associated with CRP concentrations 20 years later, even
independently of obesity and insulin resistance.

Clin Chim Acta. 2005 Apr;354(1-2):195-9. Epub 2005 Jan 11.

Long-Chain Omega6 Polyunsaturated Fatty Acids in Erythrocyte
Phospholipids Are Associated with Insulin Resistance in Non-Obese Type
2 Diabetics

BACKGROUND: Associations have been described between insulin action
and long-chain omega6 polyunsaturated fatty acids in skeletal muscle
and erythrocytes of healthy individuals. We evaluated whether there
was an association between insulin resistance and long-chain omega6
polyunsaturated fatty acids in erythrocyte phospholipids of type 2
diabetics. METHODS: Erythrocyte phospholipid fatty acid composition
was determined in 43 adult non-obese type 2 diabetics. Insulin
resistance was estimated by the HOMA mathematical approximations.
Individual omega6 fatty acids and the sum of long-chain omega6
polyunsaturated fatty acids were correlated with insulin resistance.
The same association was assessed for fatty acid product/precursor
ratios taken as measures of Delta5 desaturase, Delta6 desaturase and
their combined action. RESULTS: Except for 18:2omega6, 20:2omega6 and
20:3omega6, the individual omega6 fatty acids tested and the sum of
long-chain omega6 polyunsaturated fatty acids correlated negatively
with insulin resistance at p<0.005. Likewise, a negative correlation
was found for the combined action of Delta5 and Delta6 desaturases
(p<0.005). CONCLUSIONS: Our results indicate that formation of long-
chain omega6 fatty acids from 18:2omega6 by desaturation-elongation is
impaired under insulin resistant conditions and reduced desaturase
activities may be involved. In view of our results, we hypothesize
that in insulin resistant conditions, insulin-mediated activation of
Delta5 and Delta6 desaturases may not occur.

Can J Vet Res. 2006 Jul;70(3):191-6.

Erythrocyte and plasma fatty acid patterns in dogs with atopic
dermatitis and healthy dogs in the same household.

Recent studies have indicated that dogs with canine atopic dermatitis
(CAD) may have a disorder of fatty acid metabolism: possibly low or
absent activity of delta6-desaturase or delta5-desaturase, or both. To
clarify this possibility, we examined the erythrocyte and plasma fatty
acid patterns of 8 dogs with CAD and their 8 healthy housemates.
Atopic dermatitis was diagnosed according to the criteria proposed by
Willemse; other causes of dermatitis were excluded clinically and by
appropriate tests. Erythrocyte ghosts were prepared from blood
samples. Membrane lipids were extracted and separated by thin-layer
chromatography. From plasma and lipid fractions, fatty acid content
was determined by gas chromatography. In erythrocytes, but not in
plasma, we observed significant differences in the fatty acid pattern
that suggested a reduction in the n6 fatty acid products of the
delta6- and delta5-desaturases in dogs with atopic dermatitis when
compared with healthy housemates. Publication Types: Research Support,
Non-U.S. Gov't

Diabetologia. 1998 Nov;41(11):1337-42.

Maternal low protein diet in rats programmes fatty acid desaturase
activities in the offspring.

Numerous studies show an association between poor fetal growth and
adult insulin resistance. Recent studies have shown relation between
the long chain polyunsaturated fatty acid composition of skeletal
muscle membranes and insulin sensitivity. More detailed analysis has
indicated that the activity of delta5 desaturase is inversely
correlated to insulin resistance. The amount of docosahexaenoic acid
(C22:6n3) is also thought to play a part in determining insulin
sensitivity. The purpose of this study was to test the hypothesis that
early growth retardation in the rat, as a result of maternal protein
restriction, would lead to alterations in desaturase activities
similar to those observed in human insulin resistance. There were no
differences in phospholipid fatty acid composition in liver or muscle
from control and low protein rats. In both muscle and liver the ratio
of docosahexaenoic acid to docosapentaenoic acid was, however, reduced
in low protein offspring. Direct measurement of delta5 desaturase
activity in hepatic microsomes showed a reduction (p < 0.03) in the
low protein offspring which was negatively correlated (r = -0.855)
with fasting plasma insulin. No correlation was observed in controls.
These results show that it is possible to programme the activity of
key enzymes involved in the desaturation of long chain polyunsaturated
fatty acids. This is possibly a mechanism linking fetal growth
retardation to insulin resistance.

Lipids. 2007 Jul;42(7):629-36. Epub 2007 Jun 6.

Effects of Cigarette Smoke on Cell Viability, Linoleic Acid Metabolism
and Cholesterol Synthesis, in THP-1 Cells.

Cigarette smoke (CS) contains thousands of substances, mainly free
radicals that have as a target the polyunsaturated fatty acids (PUFA).
Long chain PUFA are produced through elongation and desaturation
reactions from their precursors; the desaturation reactions are
catalyzed by different enzymes: the conversion of 18:2n-6 (linoleic
acid, LA) to 18:3n-6 by Delta6 desaturase, while that of 20:3n-6 to
20:4n-6 by Delta5 desaturase. The aim of this work is to evaluate the
effect of serum exposed to cigarette smoke (SE-FBS) on (1) cell
viability and proliferation, (2) [1-(14)C] LA conversion and
desaturase activities in THP-1 cells, a monocytic cell line. In THP-1,
CS inhibits cell proliferation dose-dependently, by producing a
modification in the cell cycle with a reduced number of cells in
synthesis and mitosis phases at higher concentrations. CS also
decreases [1-(14)C] LA conversion to its derivatives in a
concentration-dependent manner, inhibiting the activities of Delta6
and mainly Delta5 desaturase. In addition, CS does not modify the
incorporation of LA into various lipid classes but it reduces
cholesterol synthesis from radiolabelled acetate, and increases free
fatty acid, TG and CE levels. In conclusion, CS affects lipid
metabolism, inhibiting LA conversion and desaturase activities. CS
also shifts the "de novo" lipid synthesis from free cholesterol to TG
and CE, where LA is preferentially esterified.

FEBS Lett. 2001 Nov 30;509(1):77-80.

Activity of human Delta5 and Delta6 desaturases on multiple n-3 and
n-6 polyunsaturated fatty acids.

Yeast co-expressing human elongase and desaturase genes were used to
investigate whether the same desaturase gene encodes an enzyme able to
desaturate n-3 and n-6 fatty acids with the same or different carbon
chain length. The results clearly demonstrated that a single human
Delta5 desaturase is active on 20:3n-6 and 20:4n-3. Endogenous Delta6
desaturase substrates were generated by providing to the yeast
radiolabelled 20:4n-6 or 20:5n-3 which, through two sequential
elongations, produced 24:4n-6 and 24:5n-3, respectively. Overall, our
data suggest that a single human Delta6 desaturase is active on
18:2n-6, 18:3n-3, 24:4n-6 and 24:5n-3.
monty1945@lycos.com - 28 Jun 2008 18:06 GMT
Your introductory paragraph is a bit too crowded with ideas and
doesn't "flesh them out," especially for someone who is not "up to
date" on the Mead acid information (and may have little "technical"
knowledge in this area).  Why don't you write up another summation for
your reading of these abstracts?  After all, you want to help people
in general, not just people with a strong background in a very small
scientific field, correct?
 
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