THE BETA(3)-ADRENERGIC RECEPTOR INHIBITS INSULIN-STIMULATED LEPTIN SECRETION FROM ISOLATED RAT ADIPOCYTES

Various model systems have been used to study the expression of the re cently cloned ob gene, leptin. Here we report that freshly isolated ra t white adipocytes incubated with insulin release leptin in a rapid an d concentration-dependent manner (EC(50) of 0.221 +/- .075 nM). Insuli n-stimulated leptin release could be detected as early as 30 min and a maximal 2-3 fold effect was produced by 10 nM insulin, The effect of insulin was completely blocked by simultaneous activation of cAMP-depe ndent protein kinase. Using the activation of lipolysis as an index of cAMP-dependent protein kinase activity, we show that inhibition of le ptin release by norepinephrine or the selective beta(3)-adrenergic rec eptor agonist, CL316,243, occurred in parallel to activation of cAMP-d ependent protein kinase. In addition, beta(1)- and beta(2)-adrenergic receptor antagonists did not impair the ability of norepinephrine or C L316,243 to inhibit leptin release from the adipocytes. These findings suggest that the beta(3)-adrenergic receptor plays a central role in regulating the release of leptin from the adipocyte.