Ortega, Francisco JMoreno-Navarrete, José MMayas Torres, María DoloresGarcía-Santos, EvaGómez-Serrano, MaríaRodríguez-Hermosa, José IRuiz, BartomeuRicart, WifredoTinahones, Francisco JFrühbeck, GemaPeral, BelénFernández-Real, José M2012-11-282012-11-282012-05-30Ortega FJ, Moreno-Navarrete JM, Mayas Torres MD, García-Santos E, Gómez-Serrano M, Rodriguez-Hermosa JI, et al. Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects. PLoS ONE; 7(5):e33233http://hdl.handle.net/10668/663Journal Article; Research Support, Non-U.S. Gov't;CONTEXT Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased. CONCLUSIONS The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.enRNA, MessengerAcetyl-CoA CarboxylaseBRCA1 ProteinARN MensajeroAcetil CoA CarboxilasaProteína BRCA1AdipocitosTejido AdiposoDiferenciación CelularLipogénesisMacrófagosObesidadFosforilación oxidativaCélulas 3T3-L1Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Carbon-Carbon Ligases::Acetyl-CoA CarboxylaseMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::AdipocytesMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose TissueMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::BRCA1 ProteinMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DifferentiationMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::LipogenesisMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::MacrophagesMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Phosphorylation::Oxidative PhosphorylationMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::3T3 Cells::Swiss 3T3 Cells::3T3-L1 Cellsresearch article22666314open access10.1371/journal.pone.00332331932-6203PMC3364252