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脂肪组织中的膜联蛋白:肥胖症的新角色。

Annexins in Adipose Tissue: Novel Players in Obesity.

机构信息

School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.

Department of Biomedicine, Unit of Cell Biology, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.

出版信息

Int J Mol Sci. 2019 Jul 13;20(14):3449. doi: 10.3390/ijms20143449.

Abstract

Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.

摘要

肥胖及其相关的合并症是全球日益严重的健康威胁。脂肪组织功能障碍、脂肪因子活性受损和炎症是与肥胖相关代谢疾病的核心。特别是,脂肪在脂肪组织中的过度储存会扰乱细胞内稳态。其中,细胞器功能和细胞信号转导,通常与专门膜微区(脂筏)的改变组成有关,受到影响。在这种情况下,钙(Ca)和磷脂依赖性方式与膜结合的膜联蛋白家族以调节与膜相关的事件,如内吞作用和胞吐作用以及膜微区组织的运输而广为人知。膜联蛋白的这些多种活性是通过其与大量脂质和蛋白质的多样化相互作用来促进的,这些相互作用通常发生在不同的细胞位置,并对受体、转运蛋白、代谢酶和信号复合物的活性产生影响。虽然越来越多的证据表明膜联蛋白在各种细胞和器官中的脂质稳态和细胞代谢中的功能,但它们在脂肪组织、肥胖和相关代谢疾病中的作用仍未得到很好的理解。膜联蛋白 A1(AnxA1)是一种有效的促解决介质,影响体重和代谢健康的调节。与脂肪组织中的葡萄糖代谢和脂肪酸摄取有关,几项研究表明 AnxA2 有助于协调葡萄糖转运蛋白 4(GLUT4)易位,并与脂肪酸转运蛋白 CD36 相关联。另一方面,AnxA6 与控制脂肪细胞脂肪分解和脂联素释放有关。此外,还有其他几种膜联蛋白在脂肪组织中表达,但它们在脂肪细胞中的作用尚未得到很好的研究。本文综述了膜联蛋白在脂肪细胞和肥胖中的表达研究。讨论了研究膜联蛋白在与健康和代谢疾病相关的脂肪组织中潜在作用的研究工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aba6/6678658/ef605bac766f/ijms-20-03449-g001.jpg

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