Targeting ferroptosis alleviates methionine-choline deficient (MCD)-diet induced NASH by suppressing liver lipotoxicity.

Liver International : Official Journal of the International Association for the Study of the Liver
Xiaoya LiHai-Xin Yuan

Abstract

NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression. Mice were fed on MCD-diet to mimic NASH progression and gene expression in liver was analysed by RNA-seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture. RNA-seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD-diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the...Continue Reading

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Citations

Aug 9, 2020·Frontiers in Immunology·Yongyan Chen, Zhigang Tian
Nov 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Florian GeltingerMark Rinnerthaler
Sep 23, 2020·Trends in Molecular Medicine·Marcus ConradBettina Proneth
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Dec 4, 2020·Cell Research·Daolin TangGuido Kroemer
Dec 24, 2020·International Journal of Molecular Sciences·Layla ShojaieLily Dara
Apr 6, 2021·American Journal of Physiology. Endocrinology and Metabolism·Bing LiuCaijun Rao
Jul 13, 2021·European Journal of Pharmacology·Min JiaYulong Chen
Aug 14, 2021·Frontiers in Cell and Developmental Biology·Zhilei WangZhaofang Bai
Oct 7, 2021·Cell Death Discovery·Jing WuQinghua Meng

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