title: Six-transmembrane epithelial antigen of prostate 4 and neutrophil gelatinase-associated lipocalin expression in visceral adipose tissue is related to iron status and inflammation in human obesity.
abstract: OBJECTIVE
  Six-transmembrane epithelial antigen of prostate (STEAP)-4 and neutrophil gelatinase-associated lipocalin (NGAL) are novel adipokines related to iron homeostasis with potential roles in insulin resistance and inflammation. The aim of the present work was to evaluate the effect of obesity and iron status on gene expression levels of STEAP-4 and NGAL in visceral adipose tissue (VAT) and its implication in inflammation.
  
  
  METHODS
  VAT biopsies obtained from 53 subjects were used in the study. Real-time PCR and Western-blot were performed to quantify the levels of STEAP4 and NGAL in VAT as well as the association with other genes implicated in inflammatory pathways. Circulating ferritin and free iron concentrations were also determined.
  
  
  RESULTS
  Obese patients exhibited significantly increased STEAP4 and NGAL mRNA expression levels (P < 0.001) compared to lean subjects. Protein expression levels of NGAL (P < 0.05) and STEAP4 were also higher in the visceral fat depot of obese patients, although protein levels of STEAP4 did not reach statistical significance. A negative correlation (P < 0.05) between free iron concentrations and gene expression levels of both STEAP4 and NGAL was found, while circulating ferritin concentrations were positively correlated (P < 0.05) with NGAL mRNA after body fat (BF) adjustment. Furthermore, a significant positive association between STEAP4 and NGAL gene expression levels with inflammatory markers was also detected (P < 0.01).
  
  
  CONCLUSIONS
  These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.
authors.affiliation: Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain. vcatalan@unav.es
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: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D054392:Adipokines / Q000378:metabolism; D000328:Adult; D000941:Antigens; D015992:Body Mass Index; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007501:Iron / Q000097:blood*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D054392:Adipokines; D000941:Antigens; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D007501:Iron; D010088:Oxidoreductases; C503310:STEAP4 protein, human