Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release

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. Subcutaneous and omental adipose tissue from obese, insulin-resistant dono...

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Bibliographic Details
Published in:	International Journal of Obesity 2017-12, Vol.41 (12), p.1782-1789
Main Authors:	Wentworth, J M, Zhang, J-G, Bandala-Sanchez, E, Naselli, G, Liu, R, Ritchie, M, Smyth, G K, O'Brien, P E, Harrison, L C
Format:	Article
Language:	eng
Subjects:	Abnormalities Adaptive Immunity - physiology Adipocytes Adiponectin Adiponectin - metabolism Adipose tissue Adipose tissues Antibodies Biological activity Body fat Body Mass Index Cells, Cultured Complications and side effects Conditioning Cytokines Development and progression DNA microarrays Exposure Gel filtration Genetic aspects Glucose metabolism Health aspects Humans Immunity, Innate - physiology Immunohistochemistry Inflammation Insulin Insulin - metabolism Insulin resistance Insulin Resistance - physiology Interferon Interferon gamma Interferon-gamma - metabolism Lipids Lymphocytes T Macrophages Molecular weight Neutralization Obesity Omentum - cytology Phenotype Phenotypes Physiological aspects Risk factors Stimuli Subcutaneous Fat, Abdominal - metabolism Subcutaneous Fat, Abdominal - physiopathology Trypsin γ-Interferon
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Summary:	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. 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 physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. 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 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.
ISSN:	0307-0565 1476-5497