内质网
平衡
纤维化
脂滴
脂质过氧化
肝细胞
脂质代谢
化学
细胞内
内科学
内分泌学
生物
细胞生物学
生物化学
病理
医学
氧化应激
体外
作者
Hao Jia,Juan Liu,Tinghe Fang,Zhen Zhou,Ruihong Li,Wenzhen Yin,Yao Qian,Qi Wang,Wanhui Zhou,Chang Liu,Dingcheng Sun,Xun Chen,Zheng Ouyang,Jiahong Dong,Wang Yunfang,Shuhua Yue
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-01-13
卷期号:9 (2)
标识
DOI:10.1126/sciadv.abq2937
摘要
Intracellular lipid accumulation is commonly seen in fibrotic livers, but its exact role in liver fibrosis remains elusive. Here, we established a multimodal nonlinear optical microscopy to quantitatively map distribution of biomolecules in fibrotic livers. Our data revealed that unsaturated triglycerides were predominantly accumulated in central vein area during liver fibrosis but not in portal vein area. Moreover, the lipid homeostasis was remarkably dysregulated in the late-stage compared to the early-stage fibrosis, including increased unsaturated triglycerides with decreased lipid unsaturation degree and decreased membrane fluidity. Such alterations were likely due to up-regulated lipogenesis, desaturation, and peroxidation, which consequently led to endoplasmic reticulum stress and cell death. Inspiringly, injured hepatocyte could be rescued by remodeling lipid homeostasis via either supply of unsaturated fatty acids or enhancement of membrane fluidity. Collectively, our study improves current understanding of the role of lipid homeostasis in fibrosis and open opportunities for treatment.
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