CREB activation induces adipogenesis in 3T3-L1 cells
CREB activation induces adipogenesis in 3T3-L1 cells
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DOI：
10.1128/mcb.20.3.1008-1020.2000
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发表时间：
2000-02-01
影响因子：
5.3
通讯作者：
Klemm, DJ
中科院分区：
文献类型：
--
作者：
Reusch, JEB;Colton, LA;Klemm, DJ
肥胖是许多相互作用的行为、生理和生化因素的结果。一个越来越重要的因素是，由于过量进食和/或体脂成分大幅增加，会产生额外的脂肪细胞或脂肪细胞。新脂肪细胞的生成受几种“脂肪细胞特异性”转录因子控制，这些转录因子调节前脂肪细胞增殖和脂肪形成。通常，这些脂肪细胞特异性因子仅在诱导脂肪形成后表达。参与启动脂肪细胞分化的转录因子尚未鉴定，在此我们证明转录因子CREB在前脂肪细胞中和整个分化过程中组成型表达，并且CREB受到常规分化诱导剂如胰岛素、地塞米松和二丁酰cAMP的刺激，产生稳定转染的3 T3-L1前脂肪细胞，其中我们可以诱导组成型活性CREB或CREB的表达。单独的VP 16-CREB的诱导表达足以启动脂肪形成，如通过三酰甘油储存测定的，细胞形态，以及两种脂肪细胞标记基因，过氧化物酶体增殖物激活受体γ 2和脂肪酸结合蛋白的表达。或者，KCREB单独阻断用常规分化诱导剂处理的细胞中的脂肪形成。这些数据表明CREB的活化是诱导脂肪形成所必需的且足够。最后，CREB被证明结合到几个脂肪细胞特异性基因的启动子中的假定CRE序列。这些数据坚定地确立了CREB作为脂肪形成的主要调节因子，并表明CREB可能在其他细胞和组织中发挥类似的作用。
Obesity is the result of numerous, interacting behavioral, physiological, and biochemical factors. One increasingly important factor is the generation of additional fat cells, or adipocytes, in response to excess feeding and/or large increases in body fat composition. The generation of new adipocytes is controlled by several "adipocyte-specific'' transcription factors that regulate preadipocyte proliferation and adipogenesis. Generally these adipocyte-specific factors are expressed only following the induction of adipogenesis. The transcription factor(s) that are involved in initiating adipocyte differentiation have not been identified, Here we demonstrate that the transcription factor, CREB, is constitutively expressed in preadipctcytes and throughout the differentiation process and that CREB is stimulated by conventional differentiation-inducing agents such as insulin, dexamethasone, and dibutyryl cAMP, Stably transfected 3T3-L1 preadipocytes were generated in which we could induce the expression of either a constitutively active CREB (VP16-CREB) or a dominant-negative CREB (KCREB), Inducible expression of VP16-CREB alone was sufficient to initiate adipogenesis as determined by triacylglycerol storage, cell morphology, and the expression of two adipocyte marker genes, peroxisome proliferator activated receptor gamma 2, and fatty acid binding protein. Alternatively, KCREB alone blocked adipogenesis in cells treated with conventional differentiation-inducing agents, These data indicate that activation of CREB was necessary and sufficient to induce adipogenesis. Finally, CREB was shown to bind to putative CRE sequences in the promoters of several adipocyte-specific genes. These data firmly establish CREB as a primary regulator of adipogenesis and suggest that CREB may play similar roles in other cells and tissues.