Departments of Ophthalmology, School of Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan.
Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan.
Int J Mol Sci. 2024 Jul 14;25(14):7717. doi: 10.3390/ijms25147717.
Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member of this family of proteins that are expressed in adipocytes and macrophages, plays pivotal roles in the pathogenesis of various cardiovascular and metabolic diseases, including diabetes mellitus (DM) and hypertension (HT). Since significant increases in the serum levels of FABP4 were detected in those patients, FABP4 has been identified as a crucial biomarker for these systemic diseases. In addition, in the field of ophthalmology, our group found that intraocular levels of FABP4 (ioFABP4) and free fatty acids (ioFFA) were substantially elevated in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), for which DM and HT are also recognized as significant risk factors. Recent studies have also revealed that ioFABP4 plays important roles in both retinal physiology and pathogenesis, and the results of these studies have suggested potential molecular targets for retinal diseases that might lead to future new therapeutic strategies.
脂肪酸结合蛋白(FABP)是一类参与细胞内脂质向特定细胞区室运输的脂质伴侣分子,可刺激与脂质相关的反应,如生物信号转导、膜合成、转录调控和脂质合成。先前的研究表明,FABP4 是脂肪细胞和巨噬细胞中表达的该蛋白家族的成员,在各种心血管和代谢疾病(包括糖尿病和高血压)的发病机制中发挥关键作用。由于在这些患者的血清中检测到 FABP4 水平显著升高,因此 FABP4 已被确定为这些全身性疾病的重要生物标志物。此外,在眼科学领域,我们的研究小组发现,在包括增生性糖尿病视网膜病变(PDR)和视网膜静脉阻塞(RVO)在内的视网膜血管疾病(RVD)患者的眼内液(ioFABP4 和游离脂肪酸(ioFFA)水平显著升高,而糖尿病和高血压也被认为是这些疾病的重要危险因素。最近的研究还表明,ioFABP4 在视网膜的生理和发病机制中发挥重要作用,这些研究的结果为视网膜疾病提供了潜在的分子靶点,可能为未来的新治疗策略提供依据。