Abstract
Weight gain is associated with infiltration of fat by macrophages, suggesting they are an important source of inflammation in obese adipose tissue. We have recently developed an in vitro co-culture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate. Co-culture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in marked up-regulation of pro-inflammatory cytokines such as MCP-1 and TNF-&alpha and down-regulation of anti-inflammatory cytokine adiponectin. Such inflammatory changes are induced by the co-culture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-&alpha, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-&alpha is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, FFAs may be an important adipocyte-derived mediator of inflammation in macrophages because the production of TNF-&alpha in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the co-culture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice. We postulate that a paracrine loop involving FFAs and TNF-&alpha between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. This study suggests the pathophysiologic implication of the intimate crosstalk between adipocytes and macrophages in the development of inflammatory changes in obese adipose tissue and thus the metabolic syndrome. [J Physiol Sci. 2006;56 Suppl:S56]
