Figure 10.

Proposed model for PI3K and STAT3 regulation of food intake and body weight in hypothalamic cells during endotoxemia. LPS stimulates the secretion of leptin and other cytokines in peripheral tissues. Leptin binds to its receptor in hypothalamic neurons and acutely activates the PI3K-FoxO1 pathway. Simultaneously, cytokines bind to their receptors and trigger the activation of PI3K-FoxO1 and JAK-STAT3 pathways (A). The final step in both pathways is the stimulation of the transcription of POMC, which in turn promotes reduction of food intake and body weight. Over the course of the endotoxemia, the cytokines promote a sustained activation of the JAK-STAT3 pathway, contributing to a persistent reduction of food consumption (B).