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dc.contributor.authorWentworth, JM
dc.contributor.authorNaselli, G
dc.contributor.authorBrovvn, WA
dc.contributor.authorDoyle, L
dc.contributor.authorPhipson, B
dc.contributor.authorSmyth, GK
dc.contributor.authorWabitsch, M
dc.contributor.authorO'Brien, PE
dc.contributor.authorHarrison, LC
dc.date.accessioned2021-02-04T00:28:05Z
dc.date.available2021-02-04T00:28:05Z
dc.date.issued2010-07-01
dc.identifierpii: db09-0287
dc.identifier.citationWentworth, J. M., Naselli, G., Brovvn, W. A., Doyle, L., Phipson, B., Smyth, G. K., Wabitsch, M., O'Brien, P. E. & Harrison, L. C. (2010). Pro-Inflammatory CD11c(+)CD206(+) Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity. DIABETES, 59 (7), pp.1648-1656. https://doi.org/10.2337/db09-0287.
dc.identifier.issn0012-1797
dc.identifier.urihttp://hdl.handle.net/11343/259115
dc.description.abstractOBJECTIVE: 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)-1beta, -6, -8, and -10; tumor necrosis factor-alpha; 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.
dc.languageEnglish
dc.publisherAMER DIABETES ASSOC
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titlePro-Inflammatory CD11c(+)CD206(+) Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity
dc.typeJournal Article
dc.identifier.doi10.2337/db09-0287
melbourne.affiliation.departmentMedical Education
melbourne.affiliation.departmentSchool of Mathematics and Statistics
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyScience
melbourne.source.titleDiabetes
melbourne.source.volume59
melbourne.source.issue7
melbourne.source.pages1648-1656
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1208331
melbourne.contributor.authorSmyth, Gordon
melbourne.contributor.authorHarrison, Leonard
melbourne.contributor.authorWentworth, John
dc.identifier.eissn1939-327X
melbourne.accessrightsOpen Access


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