PMID- 14569043 OWN - NLM STAT- MEDLINE DCOM- 20040720 LR - 20161124 IS - 1071-7323 (Print) IS - 1071-7323 (Linking) VI - 11 IP - 10 DP - 2003 Oct TI - Reduced expression of FOXC2 and brown adipogenic genes in human subjects with insulin resistance. PG - 1182-91 AB - OBJECTIVE: We investigated subcutaneous adipose tissue expression of FOXC2 and selected genes involved in brown adipogenesis in adult human subjects in whom we have previously identified a reduced potential of precursor cell commitment to adipose-lineage differentiation in relation to insulin resistance. RESEARCH METHODS AND PROCEDURE: Gene expression was studied using quantitative real time polymerase chain reaction. The relation between the expression of brown adipogenic genes and the genes involved in progenitor cell commitment, adipose cell size, and insulin sensitivity in vivo was analyzed. RESULTS: The expression of FOXC2, MASK, MAP3K5, retinoblastoma protein (pRb), peroxisome proliferator-activated protein gamma (PPARgamma), and retinoid X receptor gamma (RXRgamma) was decreased in the insulin-resistant compared with insulin-sensitive subjects, whereas PPARgamma-2 and CCAAT/enhancer binding protein alpha (C/EBPalpha) showed no differential expression. The FOXC2 expression correlated with that of Notch and Wnt signaling genes, as well as of the genes studied participating in brown adipogenesis, including MASK, MAP3K5, PPARgamma, pRb, RXRgamma, and PGC-1. A second-level correlation between PPARgamma and UCP-1 was also significant. In addition, the expression of MASK, MAP3K5, pRb, RXRgamma, and PGC-1 inversely correlated with adipose cell mass and also correlated with the glucose disposal rate in vivo. DISCUSSION: Our results suggest that a reduced brown adipose phenotype is associated with insulin resistance and that a basal brown adipose phenotype may be important for maintaining normal insulin sensitivity. FAU - Yang, Xiaolin AU - Yang X AD - The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska University Hospital, Goteborg, Sweden. FAU - Enerback, Sven AU - Enerback S FAU - Smith, Ulf AU - Smith U LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Obes Res JT - Obesity research JID - 9305691 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CTNNB1 protein, human) RN - 0 (Carrier Proteins) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Dishevelled Proteins) RN - 0 (FZD1 protein, human) RN - 0 (Forkhead Transcription Factors) RN - 0 (Frizzled Receptors) RN - 0 (Ion Channels) RN - 0 (Lymphoid Enhancer-Binding Factor 1) RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (NOTCH1 protein, human) RN - 0 (Phosphoproteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptor, Notch1) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Neurotransmitter) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 0 (UCP1 protein, human) RN - 0 (Uncoupling Protein 1) RN - 0 (Wnt Proteins) RN - 0 (beta Catenin) RN - 0 (mesenchyme fork head 1 protein) RN - 63231-63-0 (RNA) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Adipocytes/metabolism MH - Adipose Tissue, Brown/metabolism/*physiology MH - Biopsy MH - Carrier Proteins/genetics/metabolism MH - Cytoskeletal Proteins/genetics/metabolism MH - DNA-Binding Proteins/*biosynthesis/genetics/metabolism MH - Dishevelled Proteins MH - Forkhead Transcription Factors MH - Frizzled Receptors MH - Gene Expression Regulation/*physiology MH - Glycogen Synthase Kinase 3/genetics/metabolism MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Insulin Resistance/*genetics MH - Ion Channels MH - Lymphoid Enhancer-Binding Factor 1 MH - Male MH - Membrane Proteins/genetics/metabolism MH - Mitochondrial Proteins MH - Muscle, Skeletal/metabolism MH - Phosphoproteins/genetics/metabolism MH - Proto-Oncogene Proteins/genetics/metabolism MH - RNA/chemistry/genetics MH - Receptor, Notch1 MH - Receptors, Cell Surface/genetics/metabolism MH - Receptors, Neurotransmitter/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Statistics, Nonparametric MH - Trans-Activators/genetics/metabolism MH - Transcription Factors/*biosynthesis/genetics/metabolism MH - Uncoupling Protein 1 MH - Wnt Proteins MH - beta Catenin EDAT- 2003/10/22 05:00 MHDA- 2004/07/21 05:00 CRDT- 2003/10/22 05:00 PHST- 2003/10/22 05:00 [pubmed] PHST- 2004/07/21 05:00 [medline] PHST- 2003/10/22 05:00 [entrez] AID - 10.1038/oby.2003.163 [doi] PST - ppublish SO - Obes Res. 2003 Oct;11(10):1182-91. doi: 10.1038/oby.2003.163.