State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China.
Biochem J. 2011 Oct 1;439(1):27-38. doi: 10.1042/BJ20101475.
The factors that influence preadipocyte determination remain poorly understood. In the present paper, we report that CREBL2 [CREB (cAMP-response-element-binding protein)-like 2], a novel bZIP_1 protein, is up-regulated during MDI-induced preadipocyte differentiation. During both overexpression and under physiological conditions, CREBL2 interacted and was entirely co-localized with CREB. Overexpression of CREBL2 was sufficient to promote adipogenesis via up-regulating the expression of PPARγ (peroxisome-proliferator-activated receptor γ) and C/EBPα (CCAAT/enhancer-binding protein α) and accelerate lipogenesis accompanied with increased GLUT (glucose transporter) 1 and GLUT4. CREBL2 knockdown restrained adipogenic conversion and lipogenesis. Additionally, depletion of CREB could completely block the effects of overexpressed CREBL2, whereas an increase in CREB could not drive adipogenesis in the absence of CREBL2, indicating that the roles for CREBL2 on adipogenesis were CREB-dependent. Furthermore, siCREBL2 [siRNA (short interfering RNA) against CREBL2] could down-regulate CREB transcriptional activity and suppress CREB phosphorylation. CREB knockdown decreased the CREBL2 protein levels and vice versa. Collectively, the results of the present study indicate that CREBL2 plays a critical role in adipogenesis and lipogenesis via interaction with CREB.
影响前脂肪细胞决定的因素仍知之甚少。在本论文中，我们报告称，CREBL2（cAMP 反应元件结合蛋白样 2）是一种新型 bZIP_1 蛋白，在 MDI 诱导的前脂肪细胞分化过程中上调。在过表达和生理条件下，CREBL2 与 CREB 相互作用并完全共定位。过表达 CREBL2 足以通过上调 PPARγ（过氧化物酶体增殖物激活受体 γ）和 C/EBPα（CCAAT/增强子结合蛋白 α）的表达来促进脂肪生成，并加速伴随 GLUT1（葡萄糖转运蛋白 1）和 GLUT4 增加的脂肪生成。CREBL2 敲低抑制脂肪生成和脂肪生成。此外，耗尽 CREB 可以完全阻断过表达 CREBL2 的作用，而在没有 CREBL2 的情况下增加 CREB 不能驱动脂肪生成，表明 CREBL2 在脂肪生成中的作用依赖于 CREB。此外，siCREBL2（针对 CREBL2 的 siRNA）可以下调 CREB 转录活性并抑制 CREB 磷酸化。CREB 敲低降低了 CREBL2 蛋白水平，反之亦然。总之，本研究的结果表明，CREBL2 通过与 CREB 相互作用在脂肪生成和脂肪生成中发挥关键作用。
