The role of altered lipid composition and distribution in liver fibrosis revealed by multimodal nonlinear optical microscopy.
Sci Adv
; 9(2): eabq2937, 2023 Jan 13.
Article
en En
| MEDLINE
| ID: mdl-36638165
ABSTRACT
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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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Sci Adv
Año:
2023
Tipo del documento:
Article
País de afiliación:
China