Autor: |
Rodríguez-Cano MM; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Farmacia/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., González-Gómez MJ; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Farmacia/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., Sánchez-Solana B; National Institutes of Health, Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Monsalve EM; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina de Albacete/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., Díaz-Guerra MM; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina de Albacete/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., Laborda J; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Farmacia/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., Nueda ML; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Farmacia/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain., Baladrón V; Departamento de Química Inorgánica, Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina de Albacete/CRIB/Unidad de Biomedicina, Orgánica y Bioquímica, Universidad de Castilla-La Mancha/CSIC, C/Almansa 14, 02008 Albacete, Spain. |
Abstrakt: |
The NOTCH family of receptors and ligands is involved in numerous cell differentiation processes, including adipogenesis. We recently showed that overexpression of each of the four NOTCH receptors in 3T3-L1 preadipocytes enhances adipogenesis and modulates the acquisition of the mature adipocyte phenotype. We also revealed that DLK proteins modulate the adipogenesis of 3T3-L1 preadipocytes and mesenchymal C3H10T1/2 cells in an opposite way, despite their function as non-canonical inhibitory ligands of NOTCH receptors. In this work, we used multipotent C3H10T1/2 cells as an adipogenic model. We used standard adipogenic procedures and analyzed different parameters by using quantitative-polymerase chain reaction (qPCR), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), luciferase, Western blot, and metabolic assays. We revealed that C3H10T1/2 multipotent cells show higher levels of NOTCH receptors expression and activity and lower Dlk gene expression levels than 3T3-L1 preadipocytes. We found that the overexpression of NOTCH receptors enhanced C3H10T1/2 adipogenesis levels, and the overexpression of NOTCH receptors and DLK (DELTA-like homolog) proteins modulated the conversion of cells towards a brown-like adipocyte phenotype. These and our prior results with 3T3-L1 preadipocytes strengthen the idea that, depending on the cellular context, a precise and highly regulated level of global NOTCH signaling is necessary to allow adipogenesis and determine the mature adipocyte phenotype. |