Metabolic functions of FABPs--mechanisms and therapeutic implications.
Metabolic functions of FABPs--mechanisms and therapeutic implications.
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DOI：
10.1038/nrendo.2015.122
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Bernlohr DA
中科院分区：
文献类型：
--
作者：
Hotamisligil GS;Bernlohr DA
与蛋白质的细胞内和细胞外相互作用使脂质的功能和机制多样性成为可能。脂肪酸结合蛋白（FABPs）最初被描述为细胞内的蛋白质，可以影响细胞内的脂质流动，代谢和信号传导。随着该蛋白家族的功能被进一步阐明，很明显它们是局部和全身代谢和炎症过程的关键介质，因此是免疫代谢疾病的潜在治疗靶点。特别是，遗传缺陷和小分子介导的FABP4（也称为aP2）和FABP5的抑制可以有效地改善葡萄糖稳态并减少小鼠模型中的动脉粥样硬化。进一步的研究表明，除了它们的细胞内作用外，一些FABPs也存在于细胞外，并且FABP4经历受调节的囊泡分泌。FABP4的循环形式在全身代谢中具有重要的激素功能。在这篇综述中，我们讨论了细胞内和细胞外FABP作用的作用和调节，突出了可能指导药物发现工作和慢性代谢性疾病管理机会的新见解。
Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases.