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

Wentworth, JM; Zhang, JG; Bandala-Sanchez, E; Naselli, G; Liu, R; Ritchie, M; Smyth, GK; O&#39;Brien, PE; Harrison, LC

Author(s): Wentworth, JM; Zhang, JG; Bandala-Sanchez, E; Naselli, G; Liu, R; Ritchie, M; Smyth, GK; O'Brien, PE; Harrison, LC;
Details: Publication Year 2017,Volume 41,Issue #12,Page 1782-1789
Journal Title: International Journal of Obesity
Publication Type: Journal Article
Abstract: 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. METHODS: 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. 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 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-gamma). Recombinant human IFN-gamma recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-gamma but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-gamma released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.International Journal of Obesity advance online publication, 22 August 2017; doi:10.1038/ijo.2017.180.
Publisher: Springer Nature
Research Division(s): Population Health And Immunity; Cancer And Haematology; Molecular Medicine; Bioinformatics
PubMed ID: 28769120
Publisher's Version: https://doi.org/10.1038/ijo.2017.180
NHMRC Grants: NHMRC/1037321, NHMRC/1080887, NHMRC/1016647, NHMRC/1054618, NHMRC/1058892, NHMRC/1078106,
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Creation Date: 2017-08-30 02:22:27

Last Modified: 2018-09-21 09:04:02