Inhibition of PPARγ2 gene expression by the HIF-1-regulated gene DEC1/Stra13:: A mechanism for regulation of adipogenesis by hypoxia
Inhibition of PPARγ2 gene expression by the HIF-1-regulated gene DEC1/Stra13:: A mechanism for regulation of adipogenesis by hypoxia
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DOI：
10.1016/s1534-5807(02)00131-4
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发表时间：
2002-03-01
影响因子：
11.8
通讯作者：
Giaccia, AJ
中科院分区：
文献类型：
--
作者：
Yun, Z;Maecker, HL;Giaccia, AJ
细胞分化涉及对环境刺激的转录反应。在低氧条件下，脂肪细胞分化受到抑制，表明氧（O-2）是脂肪形成的重要生理调节因子。低氧抑制PPARgamma2核激素受体转录，低氧下PPARgamma2或C/EBPbeta的过表达刺激脂肪生成。缺乏缺氧诱导的转录因子1 α (hif -1 α)的小鼠胚胎成纤维细胞对缺氧介导的脂肪生成抑制是不耐受的。hif -1调控基因DEC1/Stra13是果蝇毛/分裂转录抑制家族的一员，可抑制PPARgamma2启动子的激活，并作为缺氧介导的脂肪生成抑制的效应因子。这些数据表明，一种o -2敏感的信号机制调节着脂肪的形成。因此，调节HIF-1活性或O-2感知的药物可用于抑制脂肪形成和控制肥胖。
Cellular differentiation involves transcriptional responses to environmental stimuli. Adipocyte differentiation is inhibited under hypoxic conditions, indicating that oxygen (O-2) is an important physiological regulator of adipogenesis. Hypoxia inhibits PPARgamma2 nuclear hormone receptor transcription, and overexpression of PPARgamma2 or C/EBPbeta stimulates adipogenesis under hypoxia. Mouse embryonic fibroblasts deficient in hypoxia-inducible transcription factor 1alpha (HIF-1alpha) are refractory to hypoxia-mediated inhibition of adipogenesis. The HIF-1-regulated gene DEC1/Stra13, a member of the Drosophila hairy/Enhancer of split transcription repressor family, represses PPARgamma2 promoter activation and functions as an effector of hypoxia-mediated inhibition of adipogenesis. These data indicate that an O-2-sensitive signaling mechanism regulates adipogenesis. Thus, agents that regulate HIF-1 activity or O-2 sensing may be used to inhibit adipogenesis and control obesity.