Schlottmann I, Ehrhart-Bornstein M, Wabitsch M, Bornstein S R, Lamounier-Zepter V
Medical Clinic III, Dresden University of Technology, Dresden, Germany.
Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University of Ulm, Germany.
Int J Obes (Lond). 2014 Sep;38(9):1221-7. doi: 10.1038/ijo.2013.241. Epub 2013 Dec 19.
Fatty acid binding protein 4 (FABP4) is a predominantly cytosolic protein of the adipocytes, but also abundantly present in human plasma; its plasma concentrations were linked to obesity and metabolic syndrome. Recent studies have suggested a direct extracellular effect of FABP4 in the regulation of glucose metabolism and heart function independently of its effect as a carrier protein. Interestingly, FABP4 has no secretory signal sequence; hence, the mechanisms how FABP4 is released from adipocytes are unclear.
In this study we investigated the mechanisms for FABP4 secretion from human adipocytes by using isolated primary pre-adipocytes (PAs) and the human adipocyte cell strain Simpson-Golabi-Behmel syndrome. In undifferentiated PAs, FABP4 expression was barely detectable and increased continuously during differentiation. The increase in FABP4 mRNA expression was accompanied by high levels of FABP4 secretion. In differentiated human adipocytes, FABP4 secretion was not abolished by blocking the Golgi-dependent secretory pathway in vitro, supporting a non-classical secretion mechanism for FABP4. However, raising intracellular Ca(2+) levels enhanced FABP4 secretion in a concentration-dependent manner.
This study shows that FABP4 is actively released from human adipocytes in vitro via a non-classical, calcium-dependent mechanism.
脂肪酸结合蛋白4（FABP4）主要是一种存在于脂肪细胞胞质中的蛋白质，但在人血浆中也大量存在；其血浆浓度与肥胖和代谢综合征有关。最近的研究表明，FABP4在调节葡萄糖代谢和心脏功能方面具有直接的细胞外作用，这与其作为载体蛋白的作用无关。有趣的是，FABP4没有分泌信号序列；因此，FABP4从脂肪细胞释放的机制尚不清楚。
在本研究中，我们使用分离的原代前脂肪细胞（PA）和人类脂肪细胞系辛普森-戈拉比-贝梅尔综合征研究了FABP4从人脂肪细胞分泌的机制。在未分化的PA中，几乎检测不到FABP4的表达，且在分化过程中持续增加。FABP4 mRNA表达的增加伴随着高水平的FABP4分泌。在分化的人脂肪细胞中，体外阻断高尔基体依赖性分泌途径并不能消除FABP4的分泌，这支持了FABP4的非经典分泌机制。然而，提高细胞内Ca(2+)水平以浓度依赖性方式增强了FABP4的分泌。
本研究表明，FABP4在体外通过非经典的、钙依赖性机制从人脂肪细胞中主动释放。
