Stable SREBP-1a knockdown decreases the cell proliferation rate in human preadipocyte cells without inducing senescence.
Sterol regulatory element binding proteins (SREBP), encoded by the Srebf1 and Srebf2 genes, are important regulators of genes involved in cholesterol and fatty acid metabolism. Whereas SREBP-2 controls the cholesterol synthesis, SREBP-1 proteins (-1a and -1c) function as the central hubs in lipid metabolism. Despite the key function of these transcription factors to promote adipocyte differentiation, the roles of SREBP-1 proteins during the preadipocyte state remain unknown. Here, we evaluate the role of SREBP-1 in preadipocyte proliferation using RNA interference technology. Knockdown of the SREBP-1a gene decreased the proliferation rate in human SGBS preadipocyte cell strain without inducing senescence. Furthermore, our data identified retinoblastoma binding protein 8 and cyclin-dependent kinase inhibitor 3 genes as new potential SREBP-1 targets, in addition to cyclin-dependent kinase inhibitor 1A which had already been described as a gene regulated by SREBP-1a. These data suggested a new role of SREBP-1 in adipogenesis via regulation of preadipocyte proliferation.
Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia, Spain.
María Soledad
MS
Alvarez
Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires C1405BWE, Argentina.
Ana
A
Fernandez-Alvarez
Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia, Spain.
Carme
C
Cucarella
Instituto de Biomedicina de Valencia (IBV-CSIC), Jaime Roig 11, E-46010 Valencia, Spain. Electronic address: mcasado@ibv.csic.es.
Marta
M
Casado
D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D034622:RNA Interference; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*
C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1
Proliferation; SGBS cells; SREBP-1; Senescence