Effects of leptin and dexamethasone on long and short leptin receptor mRNA

Background: Leptin exerts its effects by using both long (OB-Rb) and short (OB-Ra) receptors. Although leptin resistance or insensitivity is reported to be a cause of human obesity, there have not been enough studies to clarify regulation of leptin receptors. Methods: The authors studied leptin receptor regulation by leptin and dexamethasone in the human hepatocellular carcinoma cell (HepG2). Using a quantitative RT-PCR technique, the authors demonstrate expression of OB-Ra and OB-Rb mRNA after the incubation for 24 h with leptin or dexamethasone at various concentrations (10 - 9 -10 - 6 M). Results: Leptin (10 - 7 -10 - 6 M) significantly inhibited expression of OB-Rb mRNA, with maximum inhibition (43% of control) at 10 - 6 M. Expression of OB-R219.1 and OB-R219.3, two short isoforms of leptin receptor, were also reduced in cells treated with leptin most remarkably at 10 - 7 M for OB-R219.1 (44% of the control) and at 10 - 6 M for Ob-R219.3 (49% of the control). In contrast, dexamethasone (10 - 8 -10 - 6 M) significantly increased OB-Rb mRNA levels, with a maximum increase (204% of the control) at 10 - 7 M, and OB-R219.1 and OB-R219.3 mRNA expression was also markedly increased at 10 - 9 -10 - 6 M. The peak values were 254% of the control for OB-R219.1 and 246% of the control for OB-R219.3 at 10 - 7 M. Conclusions: In HepG2 cells, leptin inhibits and dexamethasone increases OB-Ra and OB-Rb mRNA expression. It is suggested that glucocorticoids as well as leptin itself contribute to regulatory effects of leptin through changes in gene expression of leptin receptors.