title: Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity.
abstract: BACKGROUND
  Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects.
  
  
  OBJECTIVE
  We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes.
  
  
  METHODS
  Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity.
  
  
  RESULTS
  We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (P<0.01) as well as in obese patients with nonalcoholic steatohepatitis (P<0.01). Furthermore, expression levels of Tnc in epididymal adipose tissue from two different mice models of obesity were significantly increased (P<0.01). TNC and TLR4 were mainly expressed by SVFC, and its expression was significantly enhanced (P<0.01) by TNF-α treatment. LPS treatment also increased mRNA levels of TNC. Moreover, the addition of exogenous TNC induced (P<0.05) TLR4 and CCL2 mRNA expression in human adipocyte cultures.
  
  
  CONCLUSIONS
  These findings indicate that TNC is involved in the etiopathology of obesity via visceral adipose tissue inflammation representing a link with ECM remodeling.
authors.affiliation: Metabolic Research Laboratory, Department of Surgery, Clínica Universidad de Navarra, Avenuda Pío XII, 36, 31008 Pamplona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Catalán
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Ambrosi
authors.forename: Amaia
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ramírez
authors.forename: Fernando
authors.initials: F
authors.lastname: Rotellar
authors.forename: Victor
authors.initials: V
authors.lastname: Valentí
authors.forename: Camilo
authors.initials: C
authors.lastname: Silva
authors.forename: María J
authors.initials: MJ
authors.lastname: Gil
authors.forename: Javier
authors.initials: J
authors.lastname: Salvador
authors.forename: Gema
authors.initials: G
authors.lastname: Frühbeck
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D005234:Fatty Liver / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D019063:Tenascin; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha