Metabolism of squalene in human fat cells. Demonstration of a two-pool system

Human adipose tissue has been shown to contain exceptionally high concentrations of squalene. In the present experiments, it was shown that most of adipose tissue squalene is located in the fat cells. Of this squalene, 80% is located in the central neutral lipid droplet and 20% is bound to the microsomal membranes. Upon incubation of isolated fat cells with radiolabeled substrates, both the microsomal and the droplet squalene became labeled. The specific activity of microsomal squalene increased faster than that of droplet squalene. In addition, the microsomal squalene quickly equilibrated to a maximal specific activity, whereas the droplet squalene showed a steady increase in specific activity. These observations indicate rapid turnover of microsomal squalene and slow turnover of droplet squalene. Moreover, they reflect intracellular transfer of labeled squalene from microsomes to the lipid droplet. During a 3-hour incubation of fat cells with labeled substrates, 90% of the newly formed labeled squalene was transferred to the lipid droplet and only 10% was converted into cholesterol. The results demonstrate that adipocyte squalene can be segregated anatomically and functionally into two distinct pools: a small metabolically active pool in the microsomal membranes where squalene is synthesized and a large metabolically inactive pool in the fat droplet where squalene is stored. The intracellular transfer of de novo synthesized squalene into the fat droplet of fat cells is one mechanism of squalene accumulation in adipose tissue.