5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) can be used as an experimental tool to activate 5'-AMP-activated protein kinase (AMPK) and has been shown to improve insulin sensitivity. In parallel adiponectin also seems to activate AMPK and to improve insulin sensitivity. We have investigated the effects of AICAR on the gene expression of adiponectin and on gene expression and release of cytokines in human adipose tissue in vitro. AICAR stimulated AMPK alpha1 activity 3-4-fold (P < 0.001), and dose-dependently increased adiponectin mRNA levels with significant stimulation (2-4-fold) at AICAR concentrations of 0.5-2 mM (p < 0.05). The adipose tissue protein release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) was decreased by AICAR (p < 0.05). In conclusion, AICAR stimulated adipose tissue AMPK alpha1 activity and adiponectin gene expression, while attenuating the release of TNF-alpha and IL-6. Reduced concentrations of these cytokines and increased levels of adiponectin might play a role for the insulin sensitizing effects of AICAR. (C) 2004 Elsevier Inc. All rights reserved.