title: Deleted in breast cancer 1 plays a functional role in adipocyte differentiation.
abstract: Genetic deletion of Dbc1 in mice reduced adipose tissue senescence and inflammation while promoting an expansion of this tissue. Here, we aimed to investigate DBC1 mRNA and protein levels in human adipose tissue from subjects with a wide spectrum of fat mass (cohort 1; n = 105) and insulin resistance (cohort 2; n = 47); we also investigated the effects of DBC1 knockdown on 3T3-L1 adipocyte differentiation. DBC1 mRNA was relatively abundant in both visceral (VAT) and subcutaneous adipose tissue (SAT) (mainly in the adipocyte fraction), being decreased in adipose tissue from obese compared with lean subjects. In both VAT and SAT, DBC1 mRNA levels were negatively associated with BMI and positively associated with age and the expression of PPARγ, GLUT4, IRS1, lipogenic (FASN, ACACA), lipid droplet-associated genes (PLIN1, FSP27, ADRP, and TIP47), and lipolytic (ABDH5, AKAP, and PRKACA) genes but negatively associated with ADIPOQ in VAT. DBC1 mRNA and protein levels were increased in the early stages of adipocyte differentiation of human and 3T3-L1 adipocytes. Dbc1 knockdown (KD) with lentivirus led to enhanced adipocyte differentiation, increasing intracellular lipid accumulation and adipogenic gene expression. In conclusion, although DBC1 gene expression was reduced in adipose tissue from obese subjects, it was negatively associated with ADIPOQ gene expression in VAT, suggesting that DBC1 might promote visceral adipose tissue dysfunction. In vitro data supported the antiadipogenic effects of DBC1.
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: María
authors: M
authors: Moreno
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: Marta
authors: M
authors: Vidal
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: Francisco
authors: F
authors: Ortega
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: Marta
authors: M
authors: Serrano
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: Gemma
authors: G
authors: Xifra
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
authors: Wifredo
authors: W
authors: Ricart
authors: Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain jmfreal@idibgi.org.
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D050152:Intra-Abdominal Fat / Q000502:physiology; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human
keywords: adipogenesis; adipose tissue; deleted in breast cancer 1; insulin sensitivity; obesity