Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using β-alanine–modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid–induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.

肝脏脂肪变性是一种广泛存在的代谢性疾病，其特征是肝脏中甘油三酯（TG）过度积累。到目前为止，有效的肝脂肪变性药物仍在开发中，从肝细胞中去除不必要的 TG 是一个巨大的挑战。在这里，我们通过使用 β-丙氨酸修饰的钆富勒烯 (GF-Ala) 纳米粒子促进肝细胞 TG 转运，探索了一种有前景的抗肝脂肪变性策略。我们证实 GF-Ala 可以逆转油酸诱导的肝细胞、果糖诱导的小鼠和肥胖相关的转基因ob/ob中的肝脂肪变性老鼠。可以观察到，GF-Ala 可改善肝肿大和肝脏脂质积累，减少脂质过氧化，并修复异常线粒体。值得注意的是，我们证明 GF-Ala 显着抑制载脂蛋白 B100 (ApoB100) 的翻译后降解，并基于其卓越的抗氧化特性促进肝细胞 TG 转运。总之，我们得出结论，GF-Ala 可以有效改善肝脏 TG 转运并维持肝脏代谢稳态而没有明显毒性，有利于治疗肝脏脂肪变性和其他脂肪肝疾病。