The concept of a chronic low-grade inflammatory status of adipose tissue during obesity is now widely accepted. This condition is regarded as a major driver for the development of cardiovascular- and diabetic complications. Macrophage recruitment and -activation is pivotal for the inflammatory process, and the different cell types and forms are involved in a complex interplay. We are investigating the regulation of intercellular communication, with special emphasis on the role of cannabinoid type-1 receptor (CB1) and CB2 mediated pathways. In order to study the effects of macrophage-secreted factors on adipocytes, 3T3-L1 adipocytes were incubated with lipopolysaccharide (LPS) or different RAW264.7 macrophage conditioned media. The release of adipokines by 3T3 cells was measured by multiplex immunoassay. Macrophage-LPS stimulated conditioned medium enhanced the adipokine secretion of especially MCP-1, PAI-1 and adiponectin, whereas release of IL-6 was lower as compared to LPS treatment. No effect on TNF-a secretion was observed. Moreover, an enhanced secretion of MCP-1 and PAI-1, but not IL-6, was measured after treatment with macrophage-stimulated conditioned medium (in absence of LPS). Macrophage conditioned medium but not LPS also increased lipolysis in 3T3-L1 cells. When studying the effects of CB1 and CB2 agonists on macrophages and adipocytes, no effects were seen so far on the TNF-a, IL-6 or IL10 secretion by macrophages stimulated with LPS. We are currently studying other ways of macrophage activation. By contrast, the cannabinoid agonist HU210 induced a 3-fold induction of triglyceride content without affecting adiponectin mRNA levels.