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 abundant in putamen, frontal lobe, medulla, cerebral cortex, cerebellum, thalamus, hippocampus, corpus callosum, caudate nucleus, and amygdala, indicating 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 increasing 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 incubation period with 50 ng/mL of leptin, compared to incubation in the absence of leptin. These results indicate that expression of Ob-Rb is differentially regulated by inhibitory signals of energy balance in neuroblastoma cells. The identification of the novel regulatory mechanisms involving the Ob-Rb isoform by insulin and leptin now makes it possible to elucidate the underlying mechanisms involving increased food intake and uncontrolled energy balance associated with leptin resistance in obese individuals.
Hikita
M
M
Second Department of Internal Medicine, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
Bujo
H
H
Hirayama
S
S
Takahashi
K
K
Morisaki
N
N
Saito
Y
Y
D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004435:Eating; D004734:Energy Metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007328:Insulin; C515448:LEPR protein, human; D020738:Leptin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin