Conjugated Linoleic Acids (CLAs) are minor components of the diet with many reported biological activities. Our aim was to examine the function of the single trans-9,trans-11 (t9,t11), cis-9,trans-11 (c9,t11), and trans-10,cis-12 (t10, c12) isomers on gene expression in human macrophages. Therefore we incubated in vitro MCSF differentiated monocyte derived macrophages from three healthy donors and THP-1 macrophages with these CLA-isomers and analyzed whole genome transcripts with Affymetrix U133 Plus 2.0 DNA-micro-arrays and real-time RT-PCR. We found that t9,t11-CLA, but not c9,t11- and t10,c12-CLA activates target genes of SREBP, SREBP-1, and ABCG1. Gene reporter assays with deletion constructs of the ABCG1 regulatory region and cotransfections with SREBP-1a and SREBP-1c expression plasmids in RAW 264.7 macrophages showed that t9,t11-CLA activates ABCG1 via SREBP-le. These results indicate that positional and geometrical isomers of CLAs have specific effects on gene expression of human macrophages and that t9,t11-CLA activates ABCG1 by a SREBP-1c-dependent mechanism. (c) 2006 Elsevier Inc. All rights reserved.