Background
Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli.
Method
Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physico-chemically, inferred by gene microarray analysis and confirmed by antibody neutralization.
Results
Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46kDa by gel filtration. SGBS adipocytes exposed to bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-g). Recombinant human IFN-g recapitulated the effects of bioactive medium and neutralizing antibody against IFN-g but not other candidate factors abrogated medium bioactivity.
Conclusion
IFN-g released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.