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Título del libro: Adipocytes: Biology, Regulation And Health Impact
Título del capítulo: Early regulation of adipogenesis: Studies in cellular models

Autores UNAM:
JORGE TONATIUH AYALA SUMUANO;
Autores externos:

Idioma:
Inglés
Año de publicación:
2012
Resumen:

White adipose tissue is a central organ in energy storage and homeostasis of the whole organism. The study of adipose differentiation has been highly facilitated by cell culture models, such as primary adipocyte cultures,the cell lines ob/ob, and the sister fibroblastic 3T3-L1 and 3T3-F442A clones. These two clones have helped to advance our knowledge on the adipose differentiation program following stimulation with adipogenic serum proteins or growth hormone, and the metabolic regulation in terminally differentiated adipocytes. The 3T3-F442A cells can also differentiate into fat pads in vivo, therefore responding to physiological signals in the body. Our studies in adipogenesis have been carried out mainly using the 3T3-F442A cells, which have high efficiency to differentiate into adipocytes. Thus, this cell line is suitable to study adipose differentiation, molecules that regulate adipogenesis, and the expression of genes involved very early in this pathway. Recently, we demonstrated that staurosporine (St) induces adipose differentiation in serum-free medium, or in the absence of adipogenic proteins. Dexamethasone (Dex) combined with St enhances adipose differentiation of 3T3-F442A cells. This model offers the following advantages: i) St/Dex promote a maximum differentiation within 4 h without any other adipogenic stimuli (incubation with adipogenic serum requires approximately 48 h for the cells to undergo adipogenesis). ii) St induces two well-defined stages for adipogenesis before clonal expansion. The first stage consists of 4 h of induction during which St induces progenitor cells to differentiate, and the second stage consists of a subsequent 44 h of stabilization, during which adipogenesis continues in the absence of the inducer but it can still be reversed by anti-adipogenic substances or cytokines. These two stages permit the identification and analysis of early gene regulation during adipogenesis. Adipose differentiation is regulated by a complex cascade of transcriptional factors. C/EBP? (gene: cebpb) activity precedes the expression of pparg2 and cebpa by several hours, raising the possibility that other genes might be expressed during such time regulating the expression of pparg2 and cebpa. The transcription factors Sterol Responsive Element Binding Proteins (SREBPs) func


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