title: Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity.
abstract: BACKGROUND
  Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT). However, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear.
  
  
  RESULTS
  Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components.
  
  
  CONCLUSIONS
  This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration associated with the development of obesity.
authors.affiliation: INSERM, UMR-S 872, Les Cordeliers, Eq, 7 Nutriomique and Eq, 13, Paris, F-75006 France. corneliu@henegar.info
authors.forename: Corneliu
authors.initials: C
authors.lastname: Henegar
authors.forename: Joan
authors.initials: J
authors.lastname: Tordjman
authors.forename: Vincent
authors.initials: V
authors.lastname: Achard
authors.forename: Danièle
authors.initials: D
authors.lastname: Lacasa
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.forename: Michèle
authors.initials: M
authors.lastname: Guerre-Millo
authors.forename: Christine
authors.initials: C
authors.lastname: Poitou
authors.forename: Arnaud
authors.initials: A
authors.lastname: Basdevant
authors.forename: Vladimir
authors.initials: V
authors.lastname: Stich
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Zucker
authors.forename: Karine
authors.initials: K
authors.lastname: Clement
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D050110:Bariatric Surgery; D005109:Extracellular Matrix / Q000473:pathology*; D005355:Fibrosis; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D015431:Weight Loss