Gregoire, Francine M., Cynthia M. Smas, and Hei Sook Sul. Understanding Adipocyte Differentiation. Physiol. Rev. 78: 783–809, 1998. — The adipocyte plays a critical role in energy balance. Adipose tissue growth involves an increase in adipocyte size and the formation of new adipocytes from precursor cells. For the last 20 years, the cellular and molecular mechanisms of adipocyte differentiation have been extensively studied using preadipocyte culture systems. Committed preadipocytes undergo growth arrest and subsequent terminal differentiation into adipocytes. This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes. Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyt...

Understanding Adipocyte Differentiation

Peroxisome Proliferator-activated Receptors α and γ Are Activated by Indomethacin and Other Non-steroidal Anti-inflammatory Drugs

RCJ 3.1, a clonally derived cell population isolated from 21-d fetal rat calvaria, expresses the osteoblast-associated characteristics of polygonal morphology, a cAMP response to parathyroid hormone, synthesis of predominantly type I collagen, and the presence of 1,25-dihydroxyvitamin D3-regulated alkaline phosphatase activity. When cultured in the presence of ascorbic acid, sodium beta-glycerophosphate, and the synthetic glucocorticoid dexamethasone, this clone differentiated in a time-dependent manner into four morphologically distinct phenotypes of known mesenchymal origin. Multinucleated muscle cells were observed as early as 9-10 d in culture, lipid-containing adipocytes formed after 12 d, chondrocyte nodules were observed after 16 d, and mineralized bone nodules formed after 21 d in culture. The differentiated cell types were characterized morphologically, histochemically, and immunohistochemically. The formation of adipocytes and chondrocytes was dependent upon the addition of dexamethasone; the muscle and bone phenotypes were also expressed at low frequency in the absence of dexamethasone. The sex steroid hormones progesterone and 17 beta-estradiol had no effect on differentiation in this system, suggesting that the effects of dexamethasone represent effects specific for glucocorticosteroids. Increasing concentrations of dexamethasone (10(-9)-10(-6) M) increased the numbers of myotubes, adipocytes, and chondrocytes; however, when present continuously for 35 d, the lower concentrations appeared to better maintain the muscle and adipocyte phenotypes. Bone nodules were not quantitated because the frequency of bone nodule formation was too low. Single cells obtained by plating RCJ 3.1 cells at limiting dilutions in the presence of dexamethasone, were shown to give rise to subclones that could differentiate into either single or multiple phenotypes. Thus, the data suggest that this clonal cell line contains subpopulations of mesenchymal progenitor cells which can, under the influence of glucocorticoid hormones, differentiate in vitro into four distinct cell types. It is, therefore, a unique cell line which will be of great use in the study of the regulation of mesenchymal stem cell differentiation.

https://rupress.org/jcb/article-pdf/106/6/2139/1056442/2139.pdf

Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone.

Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells.

S. Efthimios Polakis

Papers

Differentiation of 3T3-L1 fibroblasts to adipocytes. The effect of indomethacin, prostaglandin E1 and cyclic AMP on the process of differentiation.