|Wu, Huaizhu -|
|Perrard, Xiaoyuan -|
|Wang, Qun -|
|Perrard, Jerry -|
|Polsani, Venkateshwar -|
|Jones, Peter -|
|Smith, Wayne -|
|Ballantyne, Christie -|
Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 23, 2009
Publication Date: November 12, 2009
Citation: Wu, H., Perrard, X.D., Wang, Q., Perrard, J.L., Polsani, V.R., Jones, P.H., Smith, W.C., Ballantyne, C.M. 2009. CD11c expression in adipose tissue and blood and its role in diet-induced obesity. Arteriosclerosis Thrombosis and Vascular Biology. 30(2):186-192. Interpretive Summary: The purpose of this study was to determine the function of a protein called CD11c, which is present on the surface of some white blood cells found in fat tissues of mice on a high fat diet. This protein is also found on some white blood cells in human fat tissues. Mice genetically engineered to be deficient in this protein were placed on a high fat diet in order to cause obesity and early diabetes. The CD11c-deficient mice became as obese as normal mice on the high fat diet, but they failed to develop the inflammation of the fat tissue that occurs in normal obese mice and they failed to develop the early stages of diabetes that occurs in normal mice. These studies indicate that CD11c may be very important in causing the complications of obesity.
Technical Abstract: To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes, and blood monocytes and its role in diet-induced obesity. 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. 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.