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Critical Reviews™ in Eukaryotic Gene Expression
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ISSN Imprimir: 1045-4403
ISSN En Línea: 2162-6502

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Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukarGeneExpr.v7.i4.10
pages 281-298

Molecular Mechanisms of Adipocyte Differentiation and Inhibitory Action of Pref-1

Cynthia M. Smas
Department of Nutritional Sciences, University of California, Berkeley CA 94720
Hei Sook Sul
Department of Nutritional Sciences, University of California, Berkeley CA 94720

SINOPSIS

Commitment and differentiation of adipocytes is governed by transcription factors that are under the control of the combinatorial effects of hormonal and cell-cell and cell-matrix interaction. Established preadipocyte cell lines, such as 3T3-Ll, 3T3-F442A, and Ob 17, have made it possible to examine the molecular details of the differentiation process. Differentiation is accompanied by dramatic increases in adipocyte genes, including adipocyte fatty acid-binding protein and lipid-metabolizing enzymes. Transcription factors PPARγ and C/EBP have been shown to transactivate some of the adipocyte-expressed genes. By integrating hormonal and metabolic cues, these nuclear factors may synergistically function in adipocyte lineage determination and differentiation. Adipocyte differentiation involves drastic cell shape alterations that are accompanied by changes in expression of cytoskeletal and extracellular matrix proteins, including decreases in actin and tubulin levels. Pref-1, an EGF-repeat containing transmembrane protein, is highly expressed in preadipocytes; this expression is totally abolished after differentiation to adipocytes. Pref-1 is inhibitory for adipocyte differentiation and processing of transmembrane pref-1 generates a biologically active soluble form corresponding to the ectodomain. Interaction of the EGF-repeats of pref-1 with an as yet unidentified receptor may mediate the inhibitory effects of pref-1 in adipocyte differentiation, thereby affecting nuclear events accompanying adipogenesis.