A critical review of methods used to estimate linoleic acid˜6-desaturation ex vivo and in vivo D6-desaturase is located in a pivotal position in the metabolism of essential fatty acids (EFA). Various methods have been used to estimate D6-desaturase activity, including the assessment of: (i) tissue fatty acid compositions (and associated product/precursor ratios), (ii) D6-desaturase activities ex vivo, and (iii) isotopically labelled linoleic acid metabolism in vivo. This review critically examines these methods and considers their appropriateness and reliability in assessing linoleic acid metabolism in diabetes and cardiovascular disease.In general, there was a good agreement between the three methods and the effect of experimental diabetes on linoleic acid metabolism. In humans, however, the effect of diabetes on tissue fatty acid composition was inconsistent, and there was a paucity of data on linoleic acid metabolism ex vivo and in vivo. The inconsistency in human fatty acid compositional data may relate to variable and uncontrolled intakes of linoleic acid and its n-6 metabolites, but also to a less extreme insulin deficiency as studied in animals.Risk markers for cardiovascular disease generally reduced rat liver D6-desaturase activity ex vivo. This was not, however, reflected in tissue fatty acid compositions in these controlled studies. Linoleic acid metabolism, as determined by tissue fatty acid composition in humans, is reduced in cardiovascular disease; however, the omnivorous dietary patterns and decreased linoleic acid intakes make this conclusion potentially unreliable. Few stable-isotope studies have been conducted on the effect of cardiovascular risk markers on linoleic acid metabolism, and there is a requirement for this type of work to be standardised to facilitate inter-study comparisons. These studies may eventually help optimise EFA intake in health and disease conditions. Keywords: Linoleic acid, D6-desaturase, metabolism, indices, mammalian.
IntroductionLinoleic (C18:2 n-6) and a-linolenic acids (C18:3 n-3) are two long-chain fatty acids that are fundamental to human diets. They are termed essential fatty acids (EFA) and are converted to their respective long-chain polyunsaturated fatty acids (PUFA) in vivo by an alternating sequence of desaturation and elongation [1]. Select fatty acids of each series function as integral components of membrane phospholipids [2], as precursors of prostanoid production and in the regulation of cellular functions, including endocytosis [3] and ion channel modulation [4]. As such a lack of dietary EFA and/or their inefficient metabolism has been implicated in the aetiology and progression of diseases including cardiovascular disease (CVD) [5] and diabetes [6]. Moreover, poor cognitive development and visual function in infants have been associated with a lack of dietary EFA and their metabolism [7]. The fervent interest in the effects of genetic, dietary and endocrine factors on the metabolism of EFA throughout the lifespan has resulted in a variety of approac...