ArticleInternational journal of molecular sciences2023
PNPLA3-I148M Variant Promotes the Progression of Liver Fibrosis by Inducing Mitochondrial Dysfunction.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- A Review ofFoods (Basel, Switzerland) · 2026Review
- The I148M PNPLA3 Variant Forces Progressive Portal MASLD by Spatially Perturbing Metabolic Pathways Across Liver Zones.International journal of molecular sciences · 2026Article
- Integrated Patient Digital and Biomimetic Twins for Precision Medicine: A Perspective.Seminars in liver disease · 2025Review
- Identification of Key Genes Related to Both Lipid Metabolism Disorders and Inflammation in MAFLD.Biomedicines · 2025Article
- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Metabolic and genetic mechanisms of metabolic dysfunction-associated steatotic liver disease: an integrative perspective from molecular pathways to clinical challenges.Frontiers in endocrinology · 2025Review
- Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.Biogerontology · 2024Review
- Aging, ROS, and cellular senescence: a trilogy in the progression of liver fibrosis.Biogerontology · 2024Review
- Insulin resistance is an integral feature of MASLD even in the presence of PNPLA3 variants.JHEP reports : innovation in hepatology · 2024Article
- Article
- Comparison of wild-type and high-risk PNPLA3 variants in a human biomimetic liver microphysiology system for metabolic dysfunction-associated steatotic liver disease precision therapy.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is strongly associated with non-alcoholic steatohepatitis and advanced fibrosis; however, the underlying mechanisms remain largely unknown. In this study, we investigated the effect of PNPLA3-I148M on the activation of hepatic stellate cell line LX-2 and the progression of liver fibrosis. Immunofluorescence staining and enzyme-linked immunosorbent assay were used to detect lipid accumulation. The expression levels of fibrosis, cholesterol metabolism, and mitochondria-related markers were measured via real-time PCR or western blotting. Electron microscopy was applied to analyze the ultrastructure of the mitochondria. Mitochondrial respiration was measured by a Seahorse XFe96 analyzer. PNPLA3-I148M significantly promoted intracellular free cholesterol aggregation in LX-2 cells by decreasing cholesterol efflux protein (ABCG1) expression; it subsequently induced mitochondrial dysfunction characterized by attenuated ATP production and mitochondrial membrane potential, elevated ROS levels, caused mitochondrial structural damage, altered the oxygen consumption rate, and decreased the expression of mitochondrial-function-related proteins. Our results demonstrated for the first time that PNPLA3-I148M causes mitochondrial dysfunction of LX-2 cells through the accumulation of free cholesterol, thereby promoting the activation of LX-2 cells and the development of liver fibrosis.
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Registered trials
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