Bost F, Aouadi M, Caron L, Binétruy B
Inserm U568, Université de Nice Sophia-Antipolis, Faculté de Médecine, Avenue de Valombrose, 06107 Nice cedex, France.
Biochimie. 2005 Jan;87(1):51-6. doi: 10.1016/j.biochi.2004.10.018.
The ERK, p38 and JNK mitogen activated protein kinases (MAPKs) are intracellular signalling pathways that play a pivotal role in many essential cellular processes such as proliferation and differentiation. MAPKs are activated by a large variety of stimuli and one of their major functions is to connect cell surface receptors to transcription factors in the nucleus, which consequently triggers long-term cellular responses. This review focuses on their in vitro and in vivo roles in adipocyte differentiation and obesity. Hyperplasia of adipose tissue is a critical event for the development of obesity. Several studies have analysed the role of MAPKs in vitro in adipocyte differentiation of preadipocyte established cell lines. In the case of ERK, although the first data appeared contradictory, a consensus scenario arises: ERK would be necessary to initiate the preadipocyte into the differentiation process and, thereafter, this signal transduction pathway needs to be shut-off to proceed with adipocyte maturation. The limitation of these cellular models is that only terminal adipocyte differentiation can be analysed, eluding the early proliferative steps of adipogenesis. New insights are now emerging by investigations conducted either in vitro with the use of embryonic stem (ES) cells or in vivo with mice where these genes are invalidated. These studies not only confirm and/or precise the various functions of MAPKs in adipogenesis but, importantly, reveal unsuspected roles, for example JNK in obesity or ERK in adipogenesis of ES cells, and, for a given pathway, assign specific functions to each isoform. It appears now that a fine tuning of the MAPKs regulates both normal and pathological adipogenesis. The precise understanding of the cascade of these molecular events and the way to regulate them will be certainly crucial in order to efficiently fight obesity.
细胞外信号调节激酶（ERK）、p38和c-Jun氨基末端激酶（JNK）丝裂原活化蛋白激酶（MAPK）是细胞内信号传导通路，在许多重要的细胞过程如增殖和分化中起关键作用。MAPK可被多种刺激激活，其主要功能之一是将细胞表面受体与细胞核中的转录因子连接起来，从而触发长期的细胞反应。本综述重点关注它们在脂肪细胞分化和肥胖中的体外和体内作用。脂肪组织增生是肥胖发生的关键事件。多项研究在体外分析了MAPK在已建立的前脂肪细胞系的脂肪细胞分化中的作用。就ERK而言，尽管最初的数据似乎相互矛盾，但目前已形成一种共识：ERK对于启动前脂肪细胞进入分化过程是必需的，此后，需要关闭该信号转导通路以促进脂肪细胞成熟。这些细胞模型的局限性在于只能分析脂肪细胞的终末分化，而忽略了脂肪生成早期的增殖步骤。现在，通过使用胚胎干细胞（ES细胞）进行的体外研究或在基因无效的小鼠体内进行的研究，正在产生新的见解。这些研究不仅证实和/或明确了MAPK在脂肪生成中的各种功能，而且重要的是，揭示了一些意想不到的作用，例如JNK在肥胖中的作用或ERK在ES细胞脂肪生成中的作用，并且对于给定的信号通路，为每种异构体赋予了特定功能。现在看来，MAPK的精细调节既控制正常脂肪生成也控制病理性脂肪生成。为了有效地对抗肥胖，精确了解这些分子事件的级联反应及其调节方式肯定至关重要。
