title: DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence.
abstract: OBJECTIVE
  To investigate the possible role of deleted in breast cancer 1 (DBC1) in adipocyte and adipose tissue inflammation.
  
  
  METHODS
  In vitro knockdown experiments using shRNA-lentiviral particles were performed to investigate the effect of DBC1 on adipocyte inflammation, sirtuin 1 (Sirt1) activity, and the AMPK pathway. The relationship between DBC1 and inflammation in human adipose tissue also was examined in two independent cohorts.
  
  
  RESULTS
  Dbc1 knockdown (KD) led to a significant reduction in the expression of inflammatory genes (Tnf, Il6, Stamp2, Lbp, and Mcp1) and (pSer536) NF-κB (p65)/NF-κB (p65) ratio in fully differentiated adipocytes. Of note, Dbc1 KD increased Sirt1 and AMPK activity in the early stage of adipocyte differentiation. In morbidly obese participants, DBC1 was positively correlated to TNF and senescence (TP53 and BAX) gene expression markers in both subcutaneous and visceral adipose tissues. Multivariate regression analysis revealed that senescence-related gene markers were the best predictors of adipose tissue DBC1 mRNA levels.
  
  
  CONCLUSIONS
  DBC1 induced the expression of nuclear factor kappa B (NF-κB)-regulated inflammatory cytokines in fully differentiated 3T3-L1 adipocytes, possibly through the inhibition of Sirt1 activity, being significantly associated with human adipose tissue senescence in morbidly obese subjects.
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: María
authors: M
authors: Moreno
authors: Marta
authors: M
authors: Vidal
authors: Francisco
authors: F
authors: Ortega
authors: Wifredo
authors: W
authors: Ricart
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016922:Cellular Senescence; D015331:Cohort Studies; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D009767:Obesity, Morbid / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; C527450:CCAR2 protein, human; C000595916:KIAA1967 protein, mouse; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1