title: Switch from stress response to homeobox transcription factors in adipose tissue after profound fat loss.
abstract: BACKGROUND
  In obesity, impaired adipose tissue function may promote secondary disease through ectopic lipid accumulation and excess release of adipokines, resulting in systemic low-grade inflammation, insulin resistance and organ dysfunction. However, several of the genes regulating adipose tissue function in obesity are yet to be identified.
  
  
  RESULTS
  In order to identify novel candidate genes that may regulate adipose tissue function, we analyzed global gene expression in abdominal subcutaneous adipose tissue before and one year after bariatric surgery (biliopancreatic diversion with duodenal switch, BPD/DS) (n = 16). Adipose tissue from lean healthy individuals was also analyzed (n = 13). Two different microarray platforms (AB 1700 and Illumina) were used to measure the differential gene expression, and the results were further validated by qPCR. Surgery reduced BMI from 53.3 to 33.1 kg/m(2). The majority of differentially expressed genes were down-regulated after profound fat loss, including transcription factors involved in stress response, inflammation, and immune cell function (e.g., FOS, JUN, ETS, C/EBPB, C/EBPD). Interestingly, a distinct set of genes was up-regulated after fat loss, including homeobox transcription factors (IRX3, IRX5, HOXA5, HOXA9, HOXB5, HOXC6, EMX2, PRRX1) and extracellular matrix structural proteins (COL1A1, COL1A2, COL3A1, COL5A1, COL6A3).
  
  
  CONCLUSIONS
  The data demonstrate a marked switch of transcription factors in adipose tissue after profound fat loss, providing new molecular insight into a dichotomy between stress response and metabolically favorable tissue development. Our findings implicate homeobox transcription factors as important regulators of adipose tissue function.
authors.affiliation: Institute of Medicine, University of Bergen, Bergen, Norway.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Dankel
authors.forename: Dag J
authors.initials: DJ
authors.lastname: Fadnes
authors.forename: Anne-Kristin
authors.initials: AK
authors.lastname: Stavrum
authors.forename: Christine
authors.initials: C
authors.lastname: Stansberg
authors.forename: Rita
authors.initials: R
authors.lastname: Holdhus
authors.forename: Tuyen
authors.initials: T
authors.lastname: Hoang
authors.forename: Vivian L
authors.initials: VL
authors.lastname: Veum
authors.forename: Bjørn Jostein
authors.initials: BJ
authors.lastname: Christensen
authors.forename: Villy
authors.initials: V
authors.lastname: Våge
authors.forename: Jørn V
authors.initials: JV
authors.lastname: Sagen
authors.forename: Vidar M
authors.initials: VM
authors.lastname: Steen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors