DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence

José María Moreno-Navarrete, María Moreno, Marta Vidal, Francisco Ortega, Wifredo Ricart, José Manuel Fernández-Real*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 pSer536NF-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.

Original languageEnglish
Pages (from-to)519-522
Number of pages4
JournalObesity
Volume23
Issue number3
DOIs
Publication statusPublished - 1 Mar 2015
Externally publishedYes

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Moreno-Navarrete, J. M., Moreno, M., Vidal, M., Ortega, F., Ricart, W., & Fernández-Real, J. M. (2015). DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence. Obesity, 23(3), 519-522. https://doi.org/10.1002/oby.20999