Receptor functional analysis of leptin resistance by adenosine- BRET analysis

Leptin is an anti-obesity hormone, which circulates in the blood and acts on neuronal cells in the brain. Leptin activates the leptin receptor Ob-Rb and induces JAK2-STAT3 pathway, thus inducing an anti-obesity action. It has been suggested that most forms of obesity are accompanied by resistance to leptin, that is, insensitivity to the action of the hormone. Obesity is also accompanied by a low-grade inflammation, associated with leptin resistance. In the present study, we investigated the effect of adenosine, which is produced during inflammation, on leptin signaling. We found that adenosine can be transported into the cell and inhibit leptin-induced STAT3 phosphorylation in a neuronal cell line. On the other hand, the leptin-mediated conformational change of Ob-R, analyzed by bioluminescence resonance energy transfer (BRET), was not affected by adenosine. These results suggest that adenosine may inhibit leptin signaling by regulating signaling steps downstream of leptin receptor.