A CONSTITUTIVELY ACTIVE VERSION OF THE SER THR KINASE AKT INDUCES PRODUCTION OF THE OB GENE-PRODUCT, LEPTIN, IN 3T3-L1 ADIPOCYTES/

The expression of the oh gene product leptin in adipose tissues has be en previously described to be regulated by insulin in vivo and vitro. Akt, a ser/thr kinase with a pleckstrin homology domain, has recently been identified to function in the insulin receptor signaling cascade. The aim of this study was to investigate the role of Akt in the produ ction of leptin by adipocytes. Therefore, we examined leptin productio n by 3T3-L1 adipocytes stably expressing a myristoylated version of Ak t which is constitutively active. Leptin levels in the supernatants of serum starved, nonstimulated 3T3-L1 adipocytes were determined by rad ioimmunoassay (RIA). Expression of the constitutively active Akt was f ound to induce a more than 20-fold increase in leptin levels whereas a control non-myristoylated Akt had no effect. Leptin mRNA levels as de termined by either RNase protection assay or reverse transcriptase (RT )-polymerase chain reaction (PCR) were not elevated by the constitutiv ely active Akt. These results indicate that Akt can induce leptin prod uction in 3T3-L1 adipocytes via a non-transcriptional mechanism.