Abstract
Obese pregnant women develop severe insulin resistance and enhanced systemic and placental inflammation, suggesting associated modifications of endocrine and immune functions. Activation of innate immunity by endotoxins/lipopolysaccharides (LPS) has been proposed as a mechanism for enhancing metabolic alterations in disorders with insulin resistance. The aim of this study was to characterize the immune responses developed by the adipose tissue (AT) and their potential links to maternal endotoxemia in pregnancy with obesity. Blood and subcutaneous abdominal AT were obtained from 120 lean and obese women (term pregnancy) recruited at delivery. Gene expression was assessed in AT and stromal vascular cells isolated from a subset of 24 subjects from the same cohort. Doubling of plasma endotoxin concentrations indicated subclinical endotoxemia in obese compared with lean women. This was associated with significant increase in systemic C-reactive protein and interleukin-6 (IL-6) but not tumor necrosis factor-α (TNF-α) concentrations. AT inflammation was characterized by accumulation of CD68(+) macrophages with a threefold increased gene expression of the macrophage markers CD68, EMR1, and CD14. Gene expression for cytokines IL-6, TNF-α, IL-8, and monocyte chemotactic protein-1 (MCP1) and for LPS-sensing CD14, toll-like receptor 4 (TLR4), translocating chain-associated membrane protein 2 was 2.5-5-fold higher in stromal cells of obese compared to lean. LPS-treated cultured stromal cells of obese women expressed a 5-16-fold stimulation of the same cytokines upregulated in vivo. Our data demonstrate that subclinical endotoxemia is associated with systemic and AT inflammation in obese pregnant women. Recognition of bacterial pathogens may contribute to the combined dysfunction of innate immunity and the metabolic systems in AT.