LEPTIN INHIBITS IN-VITRO HYPOTHALAMIC SOMATOSTATIN SECRETION AND SOMATOSTATIN MESSENGER-RNA LEVELS

Leptin, the product of the ob gene, is a recently discovered hormone s ecreted by adipocytes that regulates food intake and energy expenditur e. The site of action of leptin is likely to be the hypothalamus, sinc e this area is important in the control of food intake and leptin rece ptor mRNA is particularly abundant in this area. In order to further u nravel the mechanisms by which leptin acts, we have studied the effect of leptin on in vitro somatostatin synthesis and secretion. Leptin ad ministration to fetal rat neurones in monolayer culture led to a time dependent decrease in basal somatostatin secretion and somatostatin mR NA levels, the maximal effect being observed with 6x10(-8)M leptin aft er 24 h incubation. Furthermore, leptin completely blunted 10(-7)M Neu ropeptide Y-induced increase in somatostatin secretion and somatostati n mRNA levels as well as 10.3M(Bu)(2)-cAMP and 10(-6)M A23187-induced somatostatin secretion. Finally, leptin (3x10(-8)M M) also inhibited l ow glucose (1.1 mM) induced-somatostatin secretion in perifused adult hypothalami. This data indicates that leptin can influence the neuroen docrine system by regulating hypothalamic somatostatin gene expression .