Journal Name:
Journal of Lipid Research
Article Title:
Long-chain conversion of [3C]linoleic acid and linolenic acid in response to marked changes in their dietary intake in men
Date Written:
2005
Volume:
46
Number:
0
Page:
269
Author(s):
Hussein, N.; Ah-Sing, E.; Wilkinson, P.; Leach, C.; Griffin , B.A.; Millward, D.J.
Article:
Experimental studies on the characteristics of the polyunsaturated fatty acid desaturase enzymes suggest that long-chain conversion of PUFA precursors is rate limited by the delta 6-desaturase, with competition between the n-3, n-6, and n-9 substrates for the enzyme and relative affinities varying as n-3 < n-6< n-9. This suggests that the main influences on the elongation of ALA come from competition from linoleic acid (LA) and possibly trans fatty acids.
The present study was designed to examine the long chain conversion of ALA and LA in middle-aged men with an atherogenic lipoprotein phenotype. The hypothesis studied was that a marked change in the dietary LA/ALA ratio would change the relative rates of formation of n-6:n-3 long chain PUFAs from precursor fatty acids as measured by both 13C tracer studies and through compositional changes in erythrocyte fatty acid profiles.
Subjects (38 moderately hyperlipidemic men ) were fed diets enriched with either flaxseed oil (FXO; 17 g/day ALA, n =21) or sunflower oil (SO; 17 g/day LA, n=17) for twelve weeks. *The FXO diet produced increases in phospholipid ALA (about 3-fold), eicosapentaenoic acid (EPA about 2-fold); docosapentaenoic acid (DPA about 50%) and no change in docosahexanoic acid (DHA), LA, or arachidonic acid (AA). The SO diet induced a small increase in LA but no change in AA.
Experimental studies on the characteristics of the polyunsaturated fatty acid desaturase enzymes suggest that long-chain conversion of PUFA precursors is rate limited by the delta 6-desaturase, with competition between the n-3, n-6, and n-9 substrates for the enzyme and relative affinities varying as n-3 < n-6< n-9. This suggests that the main influences on the elongation of ALA come from competition from linoleic acid (LA) and possibly trans fatty acids.
The present study was designed to examine the long chain conversion of ALA and LA in middle-aged men with an atherogenic lipoprotein phenotype. The hypothesis studied was that a marked change in the dietary LA/ALA ratio would change the relative rates of formation of n-6:n-3 long chain PUFAs from precursor fatty acids as measured by both 13C tracer studies and through compositional changes in erythrocyte fatty acid profiles.
The increased concentrations of ALA, EPA, and DPA on the FXO diet were at the expense of palmitic and oleic acids, but with only modest decreases in LA and no changes in AA at any time. There was no evidence of any inverse relationship between EPA and AA concentrations in either group, suggesting that EPA did not replace AA. The finding of a substantial increase in EPA but no change in DHA in membrane phospholipids is consistent with most but not all previous reports of ALA supplementation in adults. The highest levels of enrichment of EPA are usually achieved at the lower intakes of FXO , suggesting that high levels of ALA inhibit its conversion to EPA.
The inverse relationship between dietary ALA and the DHA content of membrane phospholipids suggests that increased ALA and/or EPA may displace DHA. The ALA/LA ratio rather than the absolute amount of ALA has been suggested to regulate the conversion to EPA, consistent with the report that doubling the intake of ALA at a constant dietary ALA/LA value had no additional influence on platelet EPA content.
The 13C results show that LCP formation from both dietary LA or ALA does vary with its relative supply and inversely in many cases with concentrations of fatty acids of the alternative series. The marked reduction in the n-6:n-3 ratio by the FXO diet resulted in a halving of [13C]LA conversion to [13C]AA and a doubling in [13C]ALA conversion to [13C]EPA compared with the high n-6:n-3 ratio SO diet.
If the delta 6-desaturase is the rate-limiting step in n-3 and n-6 LCP formation, the higher tissue concentrations of LA compared with ALA might be expected to result in higher rates of LA conversion compared with ALA, even taking into account the 1.5- to 3.0-fold higher 6-desaturase conversion rates for ALA compared with LA indicated by animal studies . However, product inhibition may be an important regulator of C18 conversion to LCPs in vivo.
In conclusion, the data indicate that reducing the dietary LA/ALA ratio downregulates LA conversion to AA and most likely upregulates ALA conversion to EPA. This suggests that the relative concentrations of the n-6 and n-3 LCP eicosanoid precursors do reflect relative dietary intakes of LA and ALA, but the relatively high background ratio of dietary n-6:n-3 tends to minimize changes in membrane AA in short-term studies.
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