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.
Vaughan
Tamisha
T
Laboratory of Innate Immunity and Inflammation, Department of Biological Sciences, Virginia Tech, Washington Street, Blacksburg, VA 24061, United States.
Li
Liwu
L
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis / Q000235:genetics; D020738:Leptin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009000:Monocytes / Q000187:drug effects*; D009765:Obesity / Q000503:physiopathology; D016133:Polymerase Chain Reaction
D020738:Leptin; D008070:Lipopolysaccharides; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse