Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata, 700032, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, Bijnor-sisendi Road, Lucknow, Uttar Pradesh, 226002, India.
Biochem Cell Biol. 2023 Jun 1;101(3):220-234. doi: 10.1139/bcb-2022-0266. Epub 2023 Feb 14.
A surfeit of mitochondrial reactive oxygen species (ROS) and inflammation serve as obligatory mediators of lipid-associated hepatocellular maladies. While retinoid homeostasis is essential in restoring systemic energy balance, its role in hepatic mitochondrial function remains elusive. The role of lecithin-retinol acyltransferase (LRAT) in maintenance of retinoid homeostasis is appreciated earlier; however, its role in modulating retinoic acid (RA) bioavailability upon lipid-imposition is unexplored. We identified LRAT overexpression in high-fat diet (HFD)-fed rats and palmitate-treated hepatoma cells. Elevation in LRAT expression depletes RA production and deregulates RA signaling. This altered RA metabolism enhances fat accumulation, accompanied by inflammation that leads to impaired mitochondrial function through enhanced ROS generation. Hence, LRAT inhibition could be a novel approach preventing lipid-induced mitochondrial dysfunction in hepatoma cells.
过量的线粒体活性氧（ROS）和炎症是脂质相关肝细胞疾病的必需介质。虽然视黄醇稳态对于恢复全身能量平衡至关重要，但它在肝线粒体功能中的作用仍不清楚。早些时候就已经认识到卵磷脂-视黄醇酰基转移酶（LRAT）在维持视黄醇稳态中的作用，但是在脂质施加时调节视黄酸（RA）生物利用度的作用尚未得到探索。我们在高脂肪饮食（HFD）喂养的大鼠和棕榈酸处理的肝癌细胞中发现了 LRAT 的过表达。LRAT 表达的升高会耗尽 RA 的产生并使 RA 信号失调。这种改变的 RA 代谢会促进脂肪积累，伴随炎症，通过增强 ROS 的产生导致线粒体功能受损。因此，LRAT 抑制可能是预防肝癌细胞中脂质诱导的线粒体功能障碍的一种新方法。
