脂肪肝
脂毒性
脂质代谢
脂肪变性
脂滴
药理学
瑞舒伐他汀
内科学
内分泌学
生物
化学
生物化学
医学
胰岛素抵抗
胰岛素
疾病
作者
Chunyan Yue,Dandan Li,Shuxin Fan,Feng Tao,Yue Yu,Wenjing Lü,Qian Chen,Ahu Yuan,Jinhui Wu,Guoping Zhao,Hong Dong,Yiqiao Hu
出处
期刊:Biomaterials
[Elsevier]
日期:2023-08-20
卷期号:301: 122291-122291
被引量:4
标识
DOI:10.1016/j.biomaterials.2023.122291
摘要
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent hepatic disease characterized as lipid accumulation, yet without any approved drug. And development of therapeutic molecules is obstructed by low efficiency and organ toxicity. Herein, we develop a long-term, low-toxic and liver-selected nano candidate, nabCK, to alleviate NAFLD. NabCK is simply composed by natural compound ginsenoside compound K (CK) and albumin. As a major metabolite of ginseng, ginsenoside CK has excellently modulating functions for lipid metabolism, but accompanied by an extremely poor bioavailability <1%. Albumin is a key lipid carrier secreted and metabolized by livers. Thereby, it can improve solubility and liver-localization of CK. In adipocytes and hepatocytes, nabCK prevents lipid deposition and eliminates lipid droplets. Transcriptomic analysis reveals that nabCK rectifies various pathways that involved in steatosis development, including lipid absorption, lipid export, fatty acid biosynthesis, lipid storage and inflammation. All these pathways are modulated by mTOR, the pivotal feedback sensor that is hyperactive in NAFLD. NabCK suppresses mTOR activation to restores lipid homeostasis. In high-fat diet (HFD) induced NAFLD mice, nabCK retards development of steatosis and fibrosis, coupling a protective effect on cardiac tissues from lipotoxicity. Together, nabCK is a safe and potent candidate to offer benefits for NAFLD treatment.
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