Isomer specific effects of Conjugated Linoleic Acid on macrophage ABCG1 transcription by a SREBP-1c dependent mechanism.
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-microarrays 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-1c. 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.
Ecker
Josef
J
Institute of Clinical Chemistry, University of Regensburg, Germany.
Langmann
Thomas
T
Moehle
Christoph
C
Schmitz
Gerd
G
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage* / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D044243:Linoleic Acids, Conjugated; D051780:Sterol Regulatory Element Binding Protein 1