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Pro-InflammatoryCD11c+CD206+ AdiposeTissue MacrophagesAre Associated WithInsulin Resistance inHuman Obesity John M. WentworthGaetano NaselliWendy A. Brown2010 год

Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity
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Аннотация: OBJECTIVE Insulin resistance and other features of the metabolic syndrome have been causally linked to adipose tissue macrophages (ATMs) in mice with diet-induced obesity. We aimed to characterize macrophage phenotype and function in human subcutaneous and omental adipose tissue in relation to insulin resistance in obesity. RESEARCH DESIGN AND METHODS Adipose tissue was obtained from lean and obese women undergoing bariatric surgery. Metabolic markers were measured in fasting serum and ATMs characterized by immunohistology, flow cytometry, and tissue culture studies. RESULTS ATMs comprised CD11c+CD206+ cells in “crown” aggregates and solitary CD11c−CD206+ cells at adipocyte junctions. In obese women, CD11c+ ATM density was greater in subcutaneous than omental adipose tissue and correlated with markers of insulin resistance. CD11c+ ATMs were distinguished by high expression of integrins and antigen presentation molecules; interleukin (IL)-1β, -6, -8, and -10; tumor necrosis factor-α; and CC chemokine ligand-3, indicative of an activated, proinflammatory state. In addition, CD11c+ ATMs were enriched for mitochondria and for RNA transcripts encoding mitochondrial, proteasomal, and lysosomal proteins, fatty acid metabolism enzymes, and T-cell chemoattractants, whereas CD11c− ATMs were enriched for transcripts involved in tissue maintenance and repair. Tissue culture medium conditioned by CD11c+ ATMs, but not CD11c− ATMs or other stromovascular cells, impaired insulin-stimulated glucose uptake by human adipocytes. CONCLUSIONS These findings identify proinflammatory CD11c+ ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c+ ATMs indicates they metabolize lipid and may initiate adaptive immune responses.
Год издания: 2010
Авторы: John M. Wentworth, Gaetano Naselli, Wendy A. Brown, Lisa Doyle, Belinda Phipson, Gordon K. Smyth, Martin Wabitsch, Paul E. O’Brien, Leonard C. Harrison
Издательство: American Diabetes Association
Источник: Diabetes
Ключевые слова: Adipokines, Inflammation, and Metabolic Diseases, Immune cells in cancer, Adipose Tissue and Metabolism
Другие ссылки: Diabetes (PDF)
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Europe PMC (PubMed Central) (PDF)
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Minerva Access (University of Melbourne) (PDF)
Minerva Access (University of Melbourne) (HTML)
PubMed Central (HTML)
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