Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity.
Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity.
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发表时间：
1999
期刊：
影响因子：
16
通讯作者：
Z. Wu;E. Rosen;R. Brun;S. Hauser;G. Adelmant;A. Troy;C. McKeon;G. Darlington;B. Spiegelman
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文献类型：
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作者：
Z. Wu;E. Rosen;R. Brun;S. Hauser;G. Adelmant;A. Troy;C. McKeon;G. Darlington;B. Spiegelman
缺乏C/EBPα的小鼠脂肪组织发育存在缺陷，但C/EBPα的确切作用尚未明确。来自C/EBPα（-/-）小鼠的成纤维细胞通过过氧化物酶体增殖物激活受体γ（PPARγ）的表达和激活进行脂肪分化，尽管存在一些明显的缺陷。缺乏C/EBPα的脂肪细胞脂质积累较少，并且它们不会诱导内源性PPARγ，这表明C/EBPα和PPARγ之间的相互调节对于维持分化状态很重要。这些细胞还显示完全没有胰岛素刺激的葡萄糖转运，这是由于胰岛素受体和胰岛素受体底物1（IRS - 1）的基因表达降低以及酪氨酸磷酸化减少所致。这些结果明确了C/EBPα在脂肪生成中的多种作用，并表明PPARγ和C/EBPα之间的相互调节是该细胞谱系转录控制的关键组成部分。
Mice deficient in C/EBP alpha have defective development of adipose tissue, but the precise role of C/EBP alpha has not been defined. Fibroblasts from C/EBP alpha(-/-) mice undergo adipose differentiation through expression and activation of PPAR gamma, though several clear defects are apparent. C/EBP alpha-deficient adipocytes accumulates less lipid, and they do not induce endogenous PPAR gamma, indicating that cross-regulation between C/EBP alpha and PPAR gamma is important in maintaining the differentiated state. The cells also show a complete absence of insulin-stimulated glucose transport, secondary to reduced gene expression and tyrosine phosphorylation for the insulin receptor and IRS-1. These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage.