Wang H Y, Malbon C C
Department of Physiology and Biophysics, University Medical Center, SUNY/Stony Brook 11794, USA
Int J Obes Relat Metab Disord. 1996 Mar;20 Suppl 3:S26-31.
Adipogenesis is the commitment of embryonic stem cells to the highly -differentiated phenotype of the adipocyte, a cell specialized to regulate, in a dynamic fashion, lipid storage. The mouse embryonic 3T3-L1 fibroblasts provide a useful model in which to probe the control differentiation in general and adipogenesis in particular. The G-proteins Gs alpha and Gi alpha 2 have been shown to modulate commitment of fibroblasts to adipocytes in response to inducers such as dexamethasone and meythylisobutylxanthine. Cellular levels of Gs alpha decline sharply in response to inducers as cells commit to the adipogenic phenotype. The molecular strategies of antisense DNA technology and expression of constitutively-activated mutants of Gi alpha 2 reveal that either suppression of Gs alpha or expression of constitutively-active Gi alpha 2 dramatically accelerate the ability of inducers to stimulate adipogenesis or act as inducers themselves. These roles of Gs alpha and Gi alpha 2 are expressed in ambient or elevated intracellular cyclic AMP, demonstrating a critical role of G-proteins in cellular differentiation independent of adenylylcyclase.
脂肪生成是胚胎干细胞向高度分化的脂肪细胞表型的转变过程，脂肪细胞是一种专门以动态方式调节脂质储存的细胞。小鼠胚胎3T3-L1成纤维细胞提供了一个有用的模型，可用于探究一般的细胞分化控制，尤其是脂肪生成的控制。G蛋白Gsα和Giα2已被证明可调节成纤维细胞对诸如地塞米松和甲基异丁基黄嘌呤等诱导剂的脂肪细胞分化。随着细胞向脂肪生成表型转变，对诱导剂的反应会使Gsα的细胞水平急剧下降。反义DNA技术的分子策略和组成型激活的Giα2突变体的表达表明，抑制Gsα或组成型激活的Giα2的表达会显著加速诱导剂刺激脂肪生成的能力，或者自身充当诱导剂。Gsα和Giα2的这些作用在细胞内环境或升高的环磷酸腺苷（cAMP）中表达，表明G蛋白在独立于腺苷酸环化酶的细胞分化中起关键作用。
