Activation of Leptin's Signaling Cascade Results in the Endocytosis of Mu Opioid Receptors

Abstract

Activation of mu opioid receptors (MOR) has been correlated with increased food intake. Obese animals show an increase in MOR receptor density in the hypothalamus. The possibility exist that changes in the expression and/or activity of MOR in obesity plays a role in the feeding behavior. Factors that contribute to the increased MOR are unknown. Thus, we sought to test the hypothesis that leptin can regulate the trafficking of MOR. We propose that under normal circumstances, leptin plays a role in the internalization of MOR which may be reflected in satiation. However, in the case of obesity, when leptin resistance develops, leptin's role in the internalization of MOR is decreased or lost such that more MOR remain at the cellular membrane and are available for activation. Human Embryonic Kidney (HEK 293) cells transfected with MOR and the leptin signaling cascade was used in these experiments. We observed that activation of leptin's signaling cascade resulted in the internalization of mu receptors. Internalization occurred after phosphorylation of serine 375. Taken together, these data demonstrate that leptin can regulate the trafficking of mu opioid receptors. Supported by DK R34‐32089