Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Nat Rev Endocrinol. 2020 Dec;16(12):697-716. doi: 10.1038/s41574-020-00418-5. Epub 2020 Oct 16.
Obesity is a health condition that has reached pandemic levels and is implicated in the development and progression of type 2 diabetes mellitus, cancer and heart failure. A key characteristic of obesity is the activation of stress-activated protein kinases (SAPKs), such as the p38 and JNK stress kinases, in several organs, including adipose tissue, liver, skeletal muscle, immune organs and the central nervous system. The correct timing, intensity and duration of SAPK activation contributes to cellular metabolic adaptation. By contrast, uncontrolled SAPK activation has been proposed to contribute to the complications of obesity. The stress kinase signalling pathways have therefore been identified as potential targets for the development of novel therapeutic approaches for metabolic syndrome. The past few decades have seen intense research efforts to determine how these kinases are regulated in a cell-specific manner and to define their contribution to the development of obesity and insulin resistance. Several studies have uncovered new and unexpected functions of the non-classical members of both pathways. Here, we provide an overview of the role of SAPKs in metabolic control and highlight important discoveries in the field.
肥胖是一种达到流行水平的健康状况，与 2 型糖尿病、癌症和心力衰竭的发展和进展有关。肥胖的一个主要特征是应激激活蛋白激酶（SAPKs）的激活，如 p38 和 JNK 应激激酶，在包括脂肪组织、肝脏、骨骼肌、免疫器官和中枢神经系统在内的几个器官中。SAPK 激活的正确时间、强度和持续时间有助于细胞代谢适应。相比之下，不受控制的 SAPK 激活被认为是肥胖并发症的原因。因此，应激激酶信号通路已被确定为代谢综合征新型治疗方法开发的潜在靶点。在过去的几十年中，人们进行了大量的研究工作，以确定这些激酶如何以细胞特异性的方式进行调节，并确定它们对肥胖和胰岛素抵抗发展的贡献。有几项研究揭示了这两条通路中非经典成员的新的和意外的功能。在这里，我们概述了 SAPK 在代谢控制中的作用，并强调了该领域的重要发现。
