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PMID: 20357360 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity.

Diabetes ·Vol. 59 ·No. 7 ·2010-07-00 ·Pages 1648-56

Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, Wabitsch M, O'Brien PE, Harrison LC

Abstract

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. 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. 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.

MeSH Terms
Adipocytes/immunology,metabolism Adipose Tissue/immunology,metabolism Analysis of Variance Body Mass Index CD11c Antigen/immunology,metabolism Cells, Cultured Female Flow Cytometry Glucose/metabolism Humans Immunohistochemistry Inflammation/immunology,metabolism Insulin/metabolism Insulin Resistance/immunology Lectins, C-Type/immunology,metabolism Macrophages/immunology,metabolism Mannose Receptor Mannose-Binding Lectins/immunology,metabolism Obesity/immunology,metabolism Oligonucleotide Array Sequence Analysis Receptors, Cell Surface/immunology,metabolism Reverse Transcriptase Polymerase Chain Reaction
Chemicals
CD11c Antigen Insulin Lectins, C-Type Mannose Receptor Mannose-Binding Lectins Receptors, Cell Surface Glucose
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wentworth John M
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Naselli Gaetano
Brown Wendy A
Doyle Lisa
Phipson Belinda
Smyth Gordon K
Wabitsch Martin
O'Brien Paul E
Harrison Leonard C
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Article Info
Journal
Diabetes
Abbr.
Diabetes
ISSN
1939-327X
DOI
10.2337/db09-0287
Published
2010-07-00
Epub
2010-00-31
Pages
1648-56
Language
English
Region
United States
NLM ID
0372763
PMCID
PMC2889764
Subset
IM
External Links
PubMed source DOI: 10.2337/db09-0287 PMC Full Text View journal details
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