CD11c expression in adipose tissue and blood and its role in diet-induced obesity.
OBJECTIVE
To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes and blood monocytes and its role in diet-induced obesity.


RESULTS
High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blood by flow cytometry, RNase protection assay, quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. Obese C57BL/6 mice had increased CD11c in AT and blood compared with lean controls. CD11c messenger RNA positively correlated with monocyte chemoattractant protein 1 in human visceral AT. Obese humans with metabolic syndrome had a higher CD11c level on blood monocytes compared with lean humans. Low-fat diet-induced weight loss reduced blood monocyte CD11c in obese mice and humans. Mouse and human monocyte CD11c levels and mouse AT CD11c messenger RNA correlated with insulin resistance. CD11c deficiency in mice did not alter weight gain but decreased inflammation, evidenced by a lower T-cell number and reduced levels of major histocompatibility complex class II, C-C chemokine ligand 2 (CCL5), CCL4, and interferon gamma in AT, and ameliorated insulin resistance and glucose intolerance associated with diet-induced obesity.


CONCLUSIONS
Diet-induced obesity increased CD11c in both AT and blood in mice and humans. CD11c plays an important role in T-cell accumulation and activation in AT, and contributes to insulin resistance associated with obesity.
Wu
Huaizhu
H
Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, Houston, Tex 77030, USA.
Perrard
Xiaoyuan Dai
XD
Wang
Qun
Q
Perrard
Jerry L
JL
Polsani
Venkateshwar R
VR
Jones
Peter H
PH
Smith
C Wayne
CW
Ballantyne
Christie M
CM
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics; D039521:CD11c Antigen / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D018925:Chemokines / Q000378:metabolism; D004038:Diet, Reducing; D004041:Dietary Fats; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018149:Glucose Intolerance / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000503:physiopathology; D007962:Leukocytes / Q000276:immunology*; D008262:Macrophage Activation; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D009765:Obesity / Q000150:complications / Q000178:diet therapy / Q000276:immunology* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D015431:Weight Loss
D015415:Biomarkers; C111835:CCL2 protein, human; D039481:CD11b Antigen; D039521:CD11c Antigen; D018932:Chemokine CCL2; D018925:Chemokines; D004041:Dietary Fats; D012333:RNA, Messenger