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.