To clarify the role of obesity in the immune responses, we investigated the relationship between insulin-induced signaling and Toll-like Receptor (TLR)-induced leukocyte cytokine secretion in obese subjects. Peripheral blood samples were collected from metabolically normal (MNO) and metabolically abnormal (MAO) obese subjects and stimulated with TLR agonists. We found elevated IL-1β, IL-10 and decreased IL-6, IFN-γ secretion in both MNO and MAO leukocytes with TLR stimulation when compared with normal leukocytes. Changes in TLR-induced cytokine secretion correlated with biochemical markers including fasting glucose, insulin, homeostasis model assessment (HOMA) index, and body mass index (BMI). Moreover, peripheral blood mononuclear cells (PBMCs) collected from MAO subjects showed enhanced basal Akt / Glycogen Synthase Kinase 3β (GSK3β) phosphorylation which was not further increased by insulin and lipopolysaccharide (LPS). We also found IκB accumulation in PBMCs isolated from normal subjects treated with GSK3β inhibitor lithium chloride. These findings indicate that TLR-induced cytokine secretion is affected by obesity even in subjects who have not reached the criteria of metabolic syndrome. Enhanced leukocyte GSK3β phosphorylation may contribute to aberrant immune response in obese subjects.
- Copyright © 2011 by The American Association of Immunologists, Inc.