PMID- 25682741 OWN - NLM STAT- MEDLINE DCOM- 20150817 LR - 20181202 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 23 IP - 3 DP - 2015 Mar TI - DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence. PG - 519-22 LID - 10.1002/oby.20999 [doi] AB - 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-kappaB (p65)/NF-kappaB (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-kappaB)-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. CI - (c) 2015 The Obesity Society. FAU - Moreno-Navarrete, Jose Maria AU - Moreno-Navarrete JM AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain. FAU - Moreno, Maria AU - Moreno M FAU - Vidal, Marta AU - Vidal M FAU - Ortega, Francisco AU - Ortega F FAU - Ricart, Wifredo AU - Ricart W FAU - Fernandez-Real, Jose Manuel AU - Fernandez-Real JM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150213 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Biomarkers) RN - 0 (CCAR2 protein, human) RN - 0 (KIAA1967 protein, mouse) RN - 0 (RNA, Messenger) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Adaptor Proteins, Signal Transducing/genetics/*metabolism MH - Adipocytes/metabolism MH - Adipose Tissue/*metabolism MH - Animals MH - Biomarkers/*metabolism MH - Cellular Senescence MH - Cohort Studies MH - Gene Expression MH - Humans MH - Inflammation/*metabolism MH - Mice MH - Obesity, Morbid/*metabolism MH - RNA, Messenger/metabolism MH - Sirtuin 1/metabolism EDAT- 2015/02/17 06:00 MHDA- 2015/08/19 06:00 CRDT- 2015/02/17 06:00 PHST- 2014/06/11 00:00 [received] PHST- 2014/11/03 00:00 [revised] PHST- 2014/11/14 00:00 [accepted] PHST- 2015/02/17 06:00 [entrez] PHST- 2015/02/17 06:00 [pubmed] PHST- 2015/08/19 06:00 [medline] AID - 10.1002/oby.20999 [doi] PST - ppublish SO - Obesity (Silver Spring). 2015 Mar;23(3):519-22. doi: 10.1002/oby.20999. Epub 2015 Feb 13.