Transient induction of ENC-1, a Kelch-related actin-binding protein, is required for adipocyte differentiation.
In an attempt to study molecules that play a regulatory role early in adipocyte differentiation, we identified by differential display ENC-1, a Drosophila kelch-related protein. ENC-1 colocalizes with actin filaments. ENC-1 is expressed in adipose tissue, specifically in the adipose-derived stroma-vascular fraction. ENC-1 mRNA levels are transiently increased 8-12-fold early in in vitro adipocyte differentiation of primary cells of the adipose-derived stroma-vascular fraction and of 3T3-L1 cells. Treatment with the adipogenic inducers dexamethasone and methylisobutylxanthine causes an increase in ENC-1 mRNA levels specifically in preadipocytes, and methylisobutylxanthine is the main effector of ENC-1 expression. The induction of ENC-1 precedes expression of the transcription factors, peroxisome proliferator-activated receptor (PPARgamma) and CCAAT/enhancer-binding protein (C/EBPalpha), and other adipocyte markers including adipocyte fatty acid-binding protein. The ENC-1 induction correlates with the subsequent differentiation of primary stroma-vascular cells into adipocytes. Furthermore, decreasing the endogenous ENC-1 levels by stable antisense transfection, thereby preventing the transient induction, effectively inhibits 3T3-L1 adipocyte differentiation. Overall, these studies indicate that ENC-1, an actin-binding protein, plays a regulatory role early in adipocyte differentiation when cytoskeletal reorganization and cell shape change from fibroblastic preadipocytes to spherical adipocytes occur.
Zhao
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Department of Nutritional Sciences, University of California, Berkeley, California 94720, USA.
Gregoire
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Sul
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides; D009687:Nuclear Proteins
D000199:Actins; D017931:DNA Primers; D008840:Microfilament Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; C112302:ectodermal-neural cortex 1 protein; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine