Allometric scaling of dietary linoleic acid on changes in tissue arachidonic acid using human equivalent diets in mice

Kylie A Weldon,Jay Whelan

doi:10.1186/1743-7075-8-43

Abstract

BackgroundIt is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation. However, levels of LA in research diets of rodents, as published in the literature, are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context.MethodsTo determine the physiological response of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was used, as opposed to differences in body weight. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (% energy) with supplemental doses of LA or AA. Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA.ResultsIncreasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, importantly recapitulating results from human trials.ConclusionsThus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption.

Highlights

It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation
It is hypothesized that metabolism of dietary AA produces bioactive compounds called eicosanoids that are positively correlated with the appreciation of tissue AA [4]
When AA was supplemented to the diets, tissue AA levels progressively increased in a dose responsive manner at the expense of LA (Figure 2 and Table 4), but tissue DHA levels did not change

Summary

Introduction

It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation. Rodent dietary composition is of particular interest in the field of nutrition research as it provides a way to assess the translational ability of individual dietary constituents, through appropriate dosing of nutrients, to physiological effects observed in humans consuming similar levels of nutrients. Dietary profiles of n-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA) and the relationship to chronic and acute diseases, in both rodents and humans, appears to lie in tissue enrichment of the downstream metabolite, arachidonic acid (AA) [1,2,3]. While the relationship of AA and eicosanoids is well established, the response to dietary LA on changes in tissue levels of AA, within the context of a human equivalent diet, remains inconclusive

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