PMID- 25648830 OWN - NLM STAT- MEDLINE DCOM- 20150612 LR - 20171116 IS - 1522-1555 (Electronic) IS - 0193-1849 (Linking) VI - 308 IP - 7 DP - 2015 Apr 1 TI - Deleted in breast cancer 1 plays a functional role in adipocyte differentiation. PG - E554-61 LID - 10.1152/ajpendo.00286.2014 [doi] AB - 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 PPARgamma, 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. CI - Copyright (c) 2015 the American Physiological Society. FAU - Moreno-Navarrete, Jose Maria AU - Moreno-Navarrete JM AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Moreno, Maria AU - Moreno M AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Vidal, Marta AU - Vidal M AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Ortega, Francisco AU - Ortega F AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Serrano, Marta AU - Serrano M AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Xifra, Gemma AU - Xifra G AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Ricart, Wifredo AU - Ricart W AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica de Girona, Centro de Investigacion Biomedica en Red Fisiopatologia de Obesidad y Nutricion (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain. FAU - Fernandez-Real, Jose Manuel AU - Fernandez-Real JM AD - Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigacio Biomedica 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150203 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CCAR2 protein, human) SB - IM MH - 3T3-L1 Cells MH - Adaptor Proteins, Signal Transducing/*physiology MH - Adipocytes/*physiology MH - Adipogenesis/*genetics MH - Adult MH - Aged MH - Animals MH - Cell Differentiation/*genetics MH - Cells, Cultured MH - Diabetes Mellitus, Type 2/genetics/metabolism MH - Gene Expression Profiling MH - Humans MH - Intra-Abdominal Fat/physiology MH - Mice MH - Middle Aged MH - Obesity/genetics/metabolism OTO - NOTNLM OT - adipogenesis OT - adipose tissue OT - deleted in breast cancer 1 OT - insulin sensitivity OT - obesity EDAT- 2015/02/05 06:00 MHDA- 2015/06/13 06:00 CRDT- 2015/02/05 06:00 PHST- 2014/06/20 00:00 [received] PHST- 2015/01/23 00:00 [accepted] PHST- 2015/02/05 06:00 [entrez] PHST- 2015/02/05 06:00 [pubmed] PHST- 2015/06/13 06:00 [medline] AID - ajpendo.00286.2014 [pii] AID - 10.1152/ajpendo.00286.2014 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2015 Apr 1;308(7):E554-61. doi: 10.1152/ajpendo.00286.2014. Epub 2015 Feb 3.