The dysregulation of fat metabolism is involved in various disorders, including neurodegenerative, cardiovascular, and cancers. The uptake of long-chain fatty acids (LCFAs) with 14 or more carbons plays a pivotal role in cellular metabolic homeostasis. Therefore, the uptake and metabolism of LCFAs must constantly be in tune with the cellular, metabolic, and structural requirements of cells. Many metabolic diseases are thought to be driven by the abnormal flow of fatty acids either from the dietary origin and/or released from adipose stores. Cellular uptake and intracellular trafficking of fatty acids are facilitated ubiquitously with unique combinations of fatty acid transport proteins and cytoplasmic fatty acid-binding proteins in every tissue. Extensive data are emerging on the defective transporters and metabolism of LCFAs and their clinical implications. Uptake and metabolism of LCFAs are crucial for the brain's functional development and cardiovascular health and maintenance. In addition, data suggest fatty acid metabolic transporter can normalize activated inflammatory response by reprogramming lipid metabolism in cancers.

Here we review the current understanding of how LCFAs and their proteins contribute to the pathophysiology of three crucial diseases and the mechanisms involved in the processes.

脂肪代谢失调与多种疾病有关，包括神经退行性疾病、心血管疾病和癌症。具有 14 个或更多碳的长链脂肪酸 (LCFA) 的摄取在细胞代谢稳态中起关键作用。因此，LCFA 的摄取和代谢必须不断与细胞的细胞、代谢和结构要求保持一致。许多代谢疾病被认为是由来自饮食来源和/或从脂肪储存释放的脂肪酸的异常流动驱动的。每个组织中脂肪酸转运蛋白和细胞质脂肪酸结合蛋白的独特组合普遍促进了脂肪酸的细胞摄取和细胞内运输。关于 LCFA 的有缺陷的转运蛋白和代谢及其临床意义的大量数据正在出现。LCFAs 的摄取和代谢对于大脑的功能发育和心血管健康与维持至关重要。此外，数据表明脂肪酸代谢转运蛋白可以通过重新编程癌症中的脂质代谢来使激活的炎症反应正常化。

在这里，我们回顾了目前对 LCFA 及其蛋白质如何促成三种关键疾病的病理生理学以及这些过程所涉及的机制的理解。