The present work indicates that there is a close inverse relationship between percentages of OA and AA acid in breast muscle lipids of chickens. The result supports our previous reports showing a similar inverse relationship between % OA and % AA in serum phospholipids of young, healthy subjects, and also found in total serum lipids of rats It would appear, therefore, that the observed inverse % OA vs. % AA relationship is a general one.
In the rat, an interaction between OA and linoleic acid, the precursor of AA, was reported several decades ago, and in a multi-center randomized cross-over study involving 200 healthy European subjects, Cicero et al. more recently showed that a 3 weeks supplementation with olive oil resulted in an increase in OA in LDL and a decrease in LA and AA. The increase in the OA/LA ratio was accompanied by reduced levels of isoprostanes, biomarkers of oxidative stress.
The finding of a negative correlation between OA and AA also in mice treated with perfluorinated fatty acids, zenobiotics used as surfactants in various industrial products, would seem in support of the contention that the inverse relationship between this couple of fatty acids exists in many species.
By pure mass action, increased supply of OA might replace AA in various compartments, such as in the lipids of cell membranes. Conceivably, increase in the percentage of one particular fatty acid must be accompanied by a reduction in the percentage of one or more of the other fatty acids. This type of mechanism was previously suggested by the results of a previous diet trial in chicken.
It has been suggested that OA is a weak competitive inhibitor of cyclooxygenase, which catalyzes conversion of the C20 PUFAs AA and EPA into prostaglandins, thromboxanes and leucotrienes, and OA might accordingly increase AA and EPA.
Another mechanism serving to explain the inverse relationship could be that OA acts as an inhibitor of Delta-5/6 desaturases and/or Elongase-5 so as to reduce the formation of AA. Additionally, the possibility exists that AA might inhibit the formation of OA by inhibition of Delta-9 desaturase. Possibly, inhibition by AA of Delta-9 desaturase gene transcription might be involved, since previous studies suggest that PUFAs of both the n6 and n3 families can inhibit this transcription. The inverse association between % OA and the AA/LA ratio, used as an estimate of AA synthesis from LA, the inverse association between % AA and the OA/Stear ratio, estimating OA synthesis, as well as the inverse association between the ratios estimating synthesis of OA and AA, respectively, i.e. the OA/Stear ratio and the AA/LA ratio, appear to be in accordance with this hypothesis.
The linear inverse association between relative abundances of OA and AA in chicken muscle lipids indicates that the OA/AA ratio may vary appreciably. Furthermore, the present multiple regression analyses suggest that ALA might at least partly govern the ratio between OA and AA in muscle lipids of chickens. The association between ALA and the OA/AA ratio prevailed with high significance when controlling for each of the several fatty acids measured. The association was attenuated when controlling for all of the fatty acids measured (Table 1, regression Model 4), as judged by the magnitude of the standardized regression coefficient. However, in this case we might have an overadjustment bias, due to control for some fatty acids which are intermediate variables (or a descending proxy for an intermediate variable) on a causal path from exposure to outcome. One example is LA which is the precursor of AA, a component of the outcome variable. On the other hand, some of the fatty acids entered among the independents may not solely be intermediates, but also serve as regulators of enzymes involved in the metabolism of fatty acids in both the n3 and n6 families. Since the regulatory function of fatty acids is not completely clarified, we have included all of the measured fatty acids in our regression analyses. Although the highly significant positive association between ALA and the OA/AA ratio prevailed also when including other fatty acids in the regression model, we cannot rule out the possibility that our results might be explained by as yet unknown covariates, and by the several inter-correlations among the fatty acids.
The observed tight positive coupling between ALA and the product/precursor estimate used for OA synthesis, as well as the strong negative association between ALA and the AA/LA ratio used to estimate AA synthesis from LA, seem to be in favor of this hypothesis. It would appear, accordingly, that one interpretation of the present results could be that the inverse % OA vs. % AA relationship is attributed not only to a direct feedback regulation between the synthesis of this couple of fatty acids, but that ALA, and possibly other fatty acids, may participate to govern the % OA vs. % AA relationship. Also our preliminary results obtained in total lipids of sera from 36 male rats suggest that ALA is positively correlated with the OA/Stear ratio (r = 0.463, p = 0.004), and negatively with the AA/LA ratio (r = -0.551, p < 0.001; results not published). Thus, one explanation of the finding that ALA was positively associated with the OA/AA ratio could be that ALA acts as a stimulator of OA synthesis and /or as an inhibitor of AA synthesis.
On the other hand, there are previous reports which apparently do not seem in support of our findings. Thus, in general, PUFAs like ALA may decrease rather than stimulate stearoyl-CoA desaturase (SCD1) expression and activity[28–32]. From these previous results we might have expected ALA to be inversely - rather than positively - related to the OA/AA and the OA/stearic acid ratios. Apparent discrepancies could possibly be related to differences in approach, for example concerning diet and species used, sex, and whether the study was done in vitro or in vivo. In any instance, the n3 PUFAs including ALA have many functions, and also as yet unknown mechanisms might be involved in their regulation.
We emphasize that the product/precursor ratio used in the present study are only crude estimates of enzyme activities, and more direct methods are needed to clarify whether the suggested mechanisms are valid.
It would appear that many of the alleged positive health effects of OA should be expected if OA acts to counteract effects of, or reduces the relative amounts of AA. Furthermore, health effects of ALA have been attributed to the fact that this fatty acid can be converted to EPA. The associations with ALA studied in the present work do not seem, however, to be explained by a similar mechanism. Since the present analyses are based upon data from a diet trial in chickens, we will not discuss possible health implications of the findings.
The present analyses were carried out on pooled data from a previously published diet trial involving several subgroups. The diets used for the present study contained 2.4% linseed oil and had equal n6/n3 ratio, but differed in amount of rendered fat, palm oil, red palm oil, and rapeseed oil. Furthermore, in some subgroups the diets had increased amount of selenium. Thus, there was a 2-fold variation between diets in the content of palmitic acid, and a 3-fold variation in the content of stearic acid. However, in spite of appreciable differences among the diets, the slope of the association curve between ALA and the OA/AA ratio remained unaffected of the diet. For example, a 2-fold increase in the intake of palmitic acid did not influence the OA vs. AA relationship.
We suggest that the consistent inverse relationship between percentages of OA and AA, possibly governed both by a direct feedback regulation between formation of OA and AA, and also influenced by ALA, could possibly be related to the risk of AA associated conditions and diseases, such as inflammation and cardiovascular diseases. However, the present data are not sufficient to substantiate this hypothesis, and further studies in man are required to examine the possibility. Whatever the mechanisms might be, the present results support our previous observation that percentages of oleic acid and arachidonic acid are inversely related.