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

BACKGROUND: 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. 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. METHODS: To 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. RESULTS: Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, importantly recapitulating results from human trials. CONCLUSIONS: Thus, 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.