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囊泡抑素作用的分子机制——从脂肪组织到皮肤和骨骼,从血管到大脑。

Molecular Mechanisms of Vaspin Action - From Adipose Tissue to Skin and Bone, from Blood Vessels to the Brain.

机构信息

Institute of Biochemistry, Faculty of Life Sciences, University of Leipzig, Leipzig, Germany.

Department of Medicine, University of Leipzig, Leipzig, Germany.

出版信息

Adv Exp Med Biol. 2019;1111:159-188. doi: 10.1007/5584_2018_241.

Abstract

Visceral adipose tissue-derived serine protease inhibitor (vaspin) or SERPINA12 according to the serpin nomenclature was identified together with other genes and gene products that were specifically expressed or overexpressed in the intra-abdominal or visceral adipose tissue (AT) of the Otsuka Long-Evans Tokushima fatty rat. These rats spontaneously develop visceral obesity, insulin resistance, hyperinsulinemia and -glycemia, as well as hypertension and thus represent a well suited animal model of obesity and related metabolic disorders such as type 2 diabetes.The follow-up study reporting the cloning, expression and functional characterization of vaspin suggested the great and promising potential of this molecule to counteract obesity induced insulin resistance and inflammation and has since initiated over 300 publications, clinical and experimental, that have contributed to uncover the multifaceted functions and molecular mechanisms of vaspin action not only in the adipose, but in many different cells, tissues and organs. This review will give an update on mechanistic and structural aspects of vaspin with a focus on its serpin function, the physiology and regulation of vaspin expression, and will summarize the latest on vaspin function in various tissues such as the different adipose tissue depots as well as the vasculature, skin, bone and the brain.

摘要

内脏脂肪组织来源的丝氨酸蛋白酶抑制剂(vaspin)或根据丝氨酸蛋白酶命名法的 SERPINA12 与其他在腹内或内脏脂肪组织(AT)中特异性表达或过表达的基因和基因产物一起被鉴定出来。这些大鼠自发地发展为内脏肥胖、胰岛素抵抗、高胰岛素血症和高血糖,以及高血压,因此代表了肥胖和相关代谢紊乱(如 2 型糖尿病)的一种非常适合的动物模型。后续的研究报告了 vaspin 的克隆、表达和功能特征,表明该分子具有对抗肥胖诱导的胰岛素抵抗和炎症的巨大和有前途的潜力,此后已经有 300 多篇临床和实验的出版物,这些出版物有助于揭示 vaspin 作用的多方面功能和分子机制,不仅在脂肪组织中,而且在许多不同的细胞、组织和器官中。这篇综述将更新 vaspin 的机制和结构方面的信息,重点介绍其丝氨酸蛋白酶抑制剂功能、vaspin 表达的生理学和调节,并总结 vaspin 在不同组织(如不同的脂肪组织储存库以及血管、皮肤、骨骼和大脑)中的最新功能。

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