A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Finland.
Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, India.
Prog Lipid Res. 2021 Jul;83:101116. doi: 10.1016/j.plipres.2021.101116. Epub 2021 Jul 20.
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。长链脂肪酸（LCFAs）的摄取（其碳链长度大于 14 个）在细胞代谢稳态中起着关键作用。因此，LCFAs 的摄取和代谢必须与细胞、代谢和结构需求保持一致。许多代谢疾病被认为是由脂肪酸异常流动引起的，这些脂肪酸要么来自饮食来源，要么从脂肪储存中释放出来。在每个组织中，脂肪酸运输蛋白和细胞质脂肪酸结合蛋白的独特组合促进了脂肪酸的细胞摄取和细胞内运输。大量数据表明，LCFAs 的转运体和代谢存在缺陷，及其临床意义。LCFAs 的摄取和代谢对大脑的功能发育和心血管健康和维持至关重要。此外，有数据表明，脂肪酸代谢转运体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，我们综述了目前对 LCFAs 及其蛋白如何导致三种重要疾病的病理生理学以及相关过程中的机制的理解。
