Cytokine production in fat tissue plays a key role in insulin resistance. The aim of study is to know the phenotypic changes of adipocytes with high fat-induced insulin resistance. High fat intake induced the expression of tumor necrosis factor alpha (TNF alpha) in visceral fat tissue as well as development of insulin resistance. Analysis of the gene expression profiles in adipocytes showed that high fat intake induced the expression of toll-like receptor 2 (TLR2) in addition to TNFa. Flow cytometry analysis revealed the presence of adipocytes co-expressing TLR2 and TNF alpha (TLR2/TNF alpha-adipocytes), and the number of TLR2/TNF alpha-adipocytes in visceral fat tissues was increased by high fat intake compared to that in subcutaneous fat tissues. Free fatty acids increased TNF alpha expression in 3T3-L1 adipocytes through TLR2 signals. These results indicate that TLR2/TNFa-adipocytes possibly cause the induction of TNF alpha expression in visceral fat tissues, being associated with the development of high fat-induced insulin resistance. (c) 2007 Elsevier Inc. All rights reserved.