ArticleRedox biology2018
Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Targeting the Gut-Liver Mitochondria Axis in MASLD: Mechanisms and Therapeutic Perspectives.Current medical science · 2026Review
- Cholic acid as a treatment for cerebrotendinous xanthomatosis: a comprehensive review of safety and efficacy.Orphanet journal of rare diseases · 2025Review
- MTFR2-Mediated Fission Drives Fatty Acid and Mitochondrial Co-Transfer from Hepatic Stellate Cells to Tumor Cells Fueling Oncogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- PlacentaAmerican journal of physiology. Endocrinology and metabolism · 2025Article
- Epithelial barrier hypothesis in the context of nutrition, microbial dysbiosis, and immune dysregulation in metabolic dysfunction-associated steatotic liver.Frontiers in immunology · 2025Review
- Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Nutrients · 2024Review
- Paradoxes: Cholesterol and Hypoxia in Preeclampsia.Biomolecules · 2024Review
- Monocyte bioenergetics: An immunometabolic perspective in metabolic dysfunction-associated steatohepatitis.Cell reports. Medicine · 2024Article
- Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation.Marine drugs · 2024Article
- Article
- Effect ofACS pharmacology & translational science · 2024Article
- Review
- Hepatic Mitochondria-Gut Microbiota Interactions in Metabolism-Associated Fatty Liver Disease.Metabolites · 2023Review
- Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.Immunity · 2023Article
- Non-alcoholic Fatty Liver Disease and Liver Fibrosis during Aging.Aging and disease · 2022Review
- Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.Molecular metabolism · 2022Article
- Hepatic Mitochondrial Dysfunction and Risk of Liver Disease in an Ovine Model of "PCOS Males".Biomedicines · 2022Article
- Sex-specific alterations in hepatic cholesterol metabolism in low birth weight adult guinea pigs.Pediatric research · 2022Article
- Clinical implications and molecular mechanisms of Cyclin-dependent kinases 4 for patients with hepatocellular carcinoma.BMC gastroenterology · 2022Article
- Implications of High-Density Cholesterol Metabolism for Oocyte Biology and Female Fertility.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.