Schwarz E J, Reginato M J, Shao D, Krakow S L, Lazar M A
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Mol Cell Biol. 1997 Mar;17(3):1552-61. doi: 10.1128/MCB.17.3.1552.
Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.
脂肪细胞分化被认为涉及转录因子C/EBPβ、过氧化物酶体增殖物激活受体γ（PPARγ）和C/EBPα的顺序诱导。C/EBPα的表达对于脂肪细胞分化既必要又充分。在此我们报告，异位表达C/EBPα或C/EBPβ均可诱导PPARγ表达和脂肪生成，并且视黄酸（RA）可通过任何一种形式的C/EBP完全抑制脂肪生成。在对正常前脂肪细胞的研究中，RA并不阻止C/EBPβ的诱导，但会阻断PPARγ、C/EBPα的诱导及脂肪生成。在瞬时转染研究中，配体化的视黄酸受体（RAR）特异性地阻断C/EBPα或C/EBPβ的转录激活。这些结果强烈表明，C/EBPα替代C/EBPβ来诱导脂肪细胞分化，并且配体化的RAR通过阻断C/EBPβ介导的下游基因诱导来抑制脂肪生成。
