Systematic name M2432
Brief description Genes up-regulated during adipogenic differentiation of 3T3-L1 cells (preadipocyte) and down-regulated by troglitazone [PubChem=5591].
Full description or abstract White adipose tissue (WAT) stores energy in the form of triglycerides, whereas brown tissue (BAT) expends energy, primarily by oxidizing lipids. WAT also secretes many cytokines and acute-phase proteins that contribute to insulin resistance in obese subjects. In this study, we have investigated the mechanisms by which activation of peroxisome proliferator-activated receptor gamma (PPARgamma) with synthetic agonists induces a brown phenotype in white adipocytes in vivo and in vitro. We demonstrate that this phenotypic conversion is characterized by repression of a set of white fat genes (visceral white), including the resistin, angiotensinogen, and chemerin genes, in addition to induction of brown-specific genes, such as Ucp-1. Importantly, the level of expression of the visceral white genes is high in mesenteric and gonadal WAT depots but low in the subcutaneous WAT depot and in BAT. Mutation of critical amino acids within helix 7 of the ligand-binding domain of PPARgamma prevents inhibition of visceral white gene expression by the synthetic agonists and therefore shows a direct role for PPARgamma in the repression process. Inhibition of the white adipocyte genes also depends on the expression of C/EBPalpha and the corepressors, carboxy-terminal binding proteins 1 and 2 (CtBP1/2). The data further show that repression of resistin and angiotensinogen expression involves recruitment of CtBP1/2, directed by C/EBPalpha, to the minimal promoter of the corresponding genes in response to the PPARgamma ligand. Developing strategies to enhance the brown phenotype in white adipocytes while reducing secretion of stress-related cytokines from visceral WAT is a means to combat obesity-associated disorders.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19564408   Authors: Vernochet C,Peres SB,Davis KE,McDonald ME,Qiang L,Wang H,Scherer PE,Farmer SR
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform MOUSE_GENE_SYMBOL
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Version history 3.1: First introduced

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