title: Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators.
abstract: Resistin is a cysteine-rich protein postulated to be a molecular link between obesity and type 2 diabetes. The aim of this study was to investigate the role of PPAR gamma in the regulation of resistin expression in human primary macrophages. Fluorescent real-time PCR (Taqman) analysis of resistin expression across a range of human tissues showed that resistin is highly expressed in bone marrow compared to other tissues. Taqman analysis and Western blotting showed that rosiglitazone decreased resistin expression at both the mRNA and protein levels in human primary monocyte-derived macrophages in vitro. Resistin expression was reduced by up to 80% after exposure to 100 nM rosiglitazone for 96 h. Bioinformatics analysis of the genomic sequence upstream of the resistin coding sequence identified several putative PPAR response elements of which one was shown to bind PPAR gamma using electrophoretic mobility shift assays. Our data support a direct role for PPAR gamma in the regulation of resistin expression.
authors.affiliation: Department of Atherosclerosis, GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK. Lisa_Patel-1@gsk.com
authors.forename: Lisa
authors.initials: L
authors.lastname: Patel
authors.forename: Amy C
authors.initials: AC
authors.lastname: Buckels
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Kinghorn
authors.forename: Paul R
authors.initials: PR
authors.lastname: Murdock
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Holbrook
authors.forename: Christopher
authors.initials: C
authors.lastname: Plumpton
authors.forename: Colin H
authors.initials: CH
authors.lastname: Macphee
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Smith
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006729:Hormones, Ectopic / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D052243:Resistin; D020218:Response Elements; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014018:Tissue Distribution; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D052243:Resistin; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone