ARACHIDONIC-ACID MALDISTRIBUTION IN OBESITY

Arachidonic acid is an important regulator of cellular function via it s effects on the physical properties of membranes, in its free form, o r as a substrate for eicosanoids. Dietary studies indicate that its pr oduction is regulated, but the mechanisms of this regulation and facto rs influencing arachidonate distribution from the site of production r emain 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 alterati ons in lipogenesis and insulin action, implying a role for arachidonat e in fuel partitioning. Evidence for this mechanism acting systemicall y has been found in genetic models of obesity in rodents and also in h umans. This review proposes that variation in the distribution of arac hidonate between phospholipid and cholesteryl ester fractions particip ates in the abnormal fuel partitioning associated with some forms of g enetic obesity.