Differential regulation of leptin receptor expression by insulin and leptin in neuroblastoma cells

Leptin exerts its effects by interacting with specific membrane receptors ( Ob-R). We studied the exact localization of long intracellular domain form (Ob-Rb) in human brain. In addition, we analyzed the regulatory features of Ob-Rb expression in two neuroblastoma cell lines. The Ob-Rb mRNAs were abu ndant in putamen, frontal lobe, medulla, cerebral cortex, cerebellum, thala mus, hippocampus, corpus callosum, caudate nucleus, and amygdala, indicatin g that Ob-Rb transcripts are expressed differently from that of other Ob-R isoforms. In SK-N-MC cells, the expression of Ob-Rb mRNA was induced by inc reasing doses of insulin, and the maximum amount of mRNA expression was 9.4 -fold higher in the presence of insulin (100 nM for 24 h), compared to the absence of insulin. In IMR32 cells, the transcripts were increased 4.0-fold when cells were incubated with 1 nM: of insulin for 48 h. In contrast, Ob- Rb expression in IMR32 cells decreased to 18% of control following a 24-h i ncubation period with 50 ng/mL of leptin, compared to incubation in the abs ence of leptin. These results indicate that expression of Ob-Rb is differen tially regulated by inhibitory signals of energy balance in neuroblastoma c ells. The identification of the novel regulatory mechanisms involving the O b-Rb isoform by insulin and leptin now makes it possible to elucidate the u nderlying mechanisms involving increased food intake and uncontrolled energ y balance associated with leptin resistance in obese individuals, (C) 2000 Academic Press.