Arachidonic acid maldistribution in obesity

Arachidonic acid is an important regulator of cellular function via its effects on the physical properties of membranes, in its free form, or as a substrate for eicosanoids. Dietary studies indicate that its production is regulated, but the mechanisms of this regulation and factors influencing arachidonate distribution from the site of production remain to be determined. In particular, whether there is a nonoxidative fate for arachidonate once it has been released from phospholipid has yet to be determined. Variations in the arachidonate content of serum, liver, and muscle lipid fractions have been correlated with alterations in lipogenesis and insulin action, implying a role for arachidonate in fuel partitioning. Evidence for this mechanism acting systemically has been found in genetic models of obesity in rodents and also in humans. This review proposes that variation in the distribution of arachidonate between phospholipid and cholesteryl ester fractions participates in the abnormal fuel partitioning associated with some forms of genetic obesity.