Transcriptional regulation of adipogenesis

ED Rosen, CJ Walkey, P Puigserver… - Genes & …, 2000 - genesdev.cshlp.org
Genes & development, 2000genesdev.cshlp.org
The past twenty years have seen great strides in our understanding of the molecular
regulation of differentiation for a whole host of specific cell types. The development of
muscle, bone, pituitary, and several hematopoeitic lineages have all been probed using a
variety of biochemical and genetic means, and such studies have yielded both general and
tissue-specific insights. Adipose tissue has also been the subject of intense scrutiny, for two
important reasons. First, the establishment of immortal preadipocyte cell lines (see below) …
The past twenty years have seen great strides in our understanding of the molecular regulation of differentiation for a whole host of specific cell types. The development of muscle, bone, pituitary, and several hematopoeitic lineages have all been probed using a variety of biochemical and genetic means, and such studies have yielded both general and tissue-specific insights. Adipose tissue has also been the subject of intense scrutiny, for two important reasons. First, the establishment of immortal preadipocyte cell lines (see below) provided an experimentally accessible system in vitro, many features of which faithfully recapitulate this process in vivo. These features include morphological changes, cessation of cell growth, expression of many lipogenic enzymes, extensive lipid accumulation, and the establishment of sensitivity to most or all of the key hormones that impact on this cell type, including insulin. The second reason why adipose tissue has received so much attention is that this tissue provides a critical link in maintaining systemic energy balance. The ongoing explosion in the incidence of obesity and its ugly stepsister, type 2 diabetes, has focused attention on all aspects of adipocyte biology, including adipogenesis (Must et al. 1999). A wealth of observations on the development of adipose tissue in vivo in a variety of species have been recorded throughout the past century. Early on it was noted that fat develops in many different sites scattered throughout the body, generally occurring in areas composed of loose connective tissue, such as the subcutaneous layers between the muscle and dermis. However, fat deposits also form around the heart, kidneys, and other internal organs. The diffuse nature of adipose differentiation in vivo has made it difficult to dissect out regions of presumptive precursor cells from embryos and study these ex vivo. Similarly, a lack of molecular markers identifying the preadipocytic state has hampered investigations in living animals.
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