Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity
Cross-regulation of C/EBPα and PPARγ controls the transcriptional pathway of adipogenesis and insulin sensitivity
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DOI：
10.1016/s1097-2765(00)80306-8
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发表时间：
1999-02-01
期刊：
影响因子：
16
通讯作者：
Spiegelman, BM
中科院分区：
文献类型：
--
作者：
Wu, ZD;Rosen, ED;Spiegelman, BM
缺乏C/EBPα的小鼠的脂肪组织发育有缺陷，但是尚未定义C/EBPα的确切作用。 C/EBPα（ - / - ）小鼠的成纤维细胞通过表达和激活PPAR伽马经历脂肪分化，尽管显而易见的是明显的缺陷。 C/EBP缺陷型脂肪细胞积聚的脂质较少，并且不会诱导内源性PPAR伽玛，这表明C/EBP Alpha和PPAR伽马之间的交叉调节对于维持差异化状态很重要。这些细胞还显示出完全没有胰岛素刺激的葡萄糖转运，其次是胰岛素受体和IRS-1的基因表达和酪氨酸磷酸化的降低，这些结果定义了脂肪形成中C/EBPα的多个作用，并显示PPARγ和C/EBP Alpha之间的交叉调节是该单元格的一个键组成部分。
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 accumulate 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.