Inflammatory Complications of Leptin

Abstract

Leptin, a key adipokine involved in regulating food intake and body weight, has been recently implicated in the exacerbation of inflammation. Elevated leptin levels are correlated with increased inflammation in obese individuals with cardiovascular complications. However, the underlying molecular mechanism is poorly understood. In this report, we demonstrated that leptin alone failed to induce the expression of inflammatory cytokines such as IL‐6 in murine macrophages and human monocytic cells. Instead, leptin significantly synergized with LPS in inducing the expression of IL‐6. The key inflammatory signaling molecule, Interleukin‐Receptor Associate Kinase 1 (IRAK‐1), is partially involved in mediating the effects of both LPS and leptin. IRAK‐1 deficient macrophages exhibit significantly lower expression of IL‐6 following LPS or LPS plus leptin stimulation. Mechanistically, we observed that leptin led to stability of IRAK‐1 both transcriptional and protein expression. Taken together, our data reveal that leptin primarily serves as a helper, instead of an initiator of inflammation during the pathogenesis of obesity related inflammatory diseases. The mechanism by which leptin mediates changes in the immune function is not known. In this present study, we aim to test the hypothesis that leptin is involved in activation proinflammatory mediators through stabilizing IRAK‐1.