Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2062-2068
Published online before print August 25, 2005, doi: 10.1161/01.ATV.0000183883.72263.13
Published online before print August 25, 2005, doi: 10.1161/01.ATV.0000183883.72263.13
© 2005 American Heart Association, Inc.
Vascular Biology |
A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes
Role of Free Fatty Acids and Tumor Necrosis Factor 
From the Department of Molecular Medicine and Metabolism (T.S., J.N., Y.O.) and the Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone (Y.O.), Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
Correspondence to Yoshihiro Ogawa, MD, Ph.D., Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 2–3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. E-mail ogawa.mmm{at}mri.tmd.ac.jp
Objective— Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate.
Methods and Results— Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor (TNF-), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF- is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF- in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice.
Conclusions— We postulate that a paracrine loop involving FFAs and TNF- between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue.
We developed an in vitro coculture system composed of adipocytes and macrophages to elucidate the functional interaction between these cells. The data suggest that a paracrine loop involving FFAs and TNF- derived from adipocytes and macrophages, respectively, establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue
Key Words: macrophage • adipocyte • fatty acids • TNF- • obesity
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