Molecular mechanism underlying the inflammatory complication of leptin in macrophages

Leptin a key adipokine involved in regulating food Intake and body weight has been recently implicated in the exacerbation of inflammation Elevated leptin levels in blood circulation 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 augment the effect of 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 increases the expression of IRAK-1 in both human monocytes and murine macrophages Taken together our data reveal that leptin primarily serves as a helper instead of an initiator of inflammation during the pathogenesis of obesity-related inflammation (C) 2010 Elsevier Ltd All rights reserved