Context: Chronic inflammation converges in type 2 diabetes and atherosclerosis. Modulation of adipokine signaling by innate immunity in humans is of considerable interest given the role of adipokines in insulin resistance and atherosclerosis.

Objective: To examine effects of low grade endotoxemia, a model of human inflammation, on adipokine signaling in vivo.

Design: Open-label, placebo-controlled, fixed-sequence clinical study.

Setting: General Clinical Research Center.

Patients: Twenty healthy male (50%) and female volunteers aged 18-40.

Intervention: Serial blood sampling and adipose biopsies for 24 hours before and after intravenous bolus endotoxin (LPS, 3 ng/kg).

Main Outcome Measures: Plasma leptin, adiponectin, resistin, soluble leptin receptor, cytokines, insulin and glucose; distribution of adiponectin among multimeric complexes; whole blood, monocyte and adipose mRNA for adipokines and their receptors.

Results: LPS induced fever, blood and adipose TNF and IL6, and increased HOMA-IR. These were associated with increases in plasma leptin (from 4.1±1.1 to 6.1±1.9 ng/ml in men; 21.1±4.4 to 27.4±4.7 ng/ml in women, p<0.005), doubling of leptin:soluble leptin receptor ratio, and marked induction of whole blood resistin mRNA (13.7±7.3-fold, p<0.001) and plasma resistin (8.5±2.75 to 43.2±15.3 ng/ml, p<0.001). Although total adiponectin levels and low and high molecular weight adiponectin complexes were unaltered by LPS treatment, whole blood mRNA for adiponectin receptors, ADIPOR1 (49%, p<0.005) and ADIPOR2 (65%, p<0.001), was suppressed.

Conclusions: Modulation of adipokine signaling may contribute to the insulin resistant, atherogenic state associated with human inflammatory syndromes. Targeting of individual adipokines or their upstream regulation may prove effective in preventing acute and chronic inflammation-related metabolic complications.