Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression
| العنوان: | Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression |
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| المؤلفون: | Giuseppe Poli, Maria Blonda, Giorgia di Bello, Luigi Iuliano, Gaetano Serviddio, Gianluigi Vendemiale, Carlo Avolio, Giuseppina Iannelli, Antonio Facciorusso, Rosanna Tamborra, Francesco Bellanti, Rosanna Villani |
| المصدر: | Redox Biology, Vol 15, Iss C, Pp 86-96 (2018) Redox Biology |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, MMP, mitochondrial membrane potential, 5α, 6α-epoxy, 5α,6α-epoxycholesterol, Clinical Biochemistry, HF+HCh, high-fat+high-cholesterol, Respiratory chain, Apoptosis, Mitochondria, Liver, Mitochondrion, medicine.disease_cause, Biochemistry, SDM, standard deviation of the mean, cholesterol excess, fatty acids, mitochondria, non-alcoholic fatty liver disease, oxysterols, Nonalcoholic fatty liver disease, lcsh:QH301-705.5, ANOVA, analysis of variance, TNF, tumor necrosis factor, lcsh:R5-920, Chemistry, UCP2, uncoupling protein 2, Oxysterols, Cholesterol excess, Mitochondria, Mitochondrial respiratory chain, Lipotoxicity, Liver, CTRL, control, Disease Progression, lipids (amino acids, peptides, and proteins), FFAs, free fatty acids, lcsh:Medicine (General), Oxidation-Reduction, Research Paper, medicine.medical_specialty, NAFLD, non-alcoholic fatty liver disease, NASH, non-alcoholic steatohepatitis, Diet, High-Fat, 03 medical and health sciences, PA, palmitic acid, Δψ, mitochondrial membrane potential, HF, high-fat, Internal medicine, medicine, NAFL, non-alcoholic fatty liver, Humans, 5β, 6β-epoxy, 5β,6β-epoxycholesterol, Fatty acids, PGC1α, peroxisome proliferator-activated receptor-γ coactivator 1 α, TFAM, mitochondrial transcription factor A, NRF1, nuclear respiratory factor 1, Organic Chemistry, 6-oxo, 6-oxo-cholestan-3β,5α-diol, OA, oleic acid, CT, threshold cycle, medicine.disease, Lipid Metabolism, mtDNA, mitochondrial DNA, Oxidative Stress, 030104 developmental biology, Endocrinology, triol, 5α-cholestane-3β,5,6β-triol, Mitochondrial biogenesis, BN-PAGE, Blue Native bidimensional polyacrylamide gel electrophoresis, lcsh:Biology (General), Hepatocytes, 7β-OHC, 7β-hydroxycholesterol, Steatohepatitis, Reactive Oxygen Species, Oxidative stress, 7KC, 7-ketocholesterol, CYPs, cytochromes P450, Non-alcoholic fatty liver disease |
| الوصف: | 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. Graphical abstract fx1 Highlights • Mitochondrial adaptation in NAFLD is lost in fatty acids + cholesterol-induced NASH. • Fatty acids + oxysterols alter mitochondria function/biogenesis inducing cell death. • Mitochondria respiratory proteins and biogenesis regulators are lower in human NASH. • Fatty acids and oxysterols interaction may explain mitochondria dysfunction in NASH. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b13897abda95ce40fb1e631f0e1a131eTest http://www.sciencedirect.com/science/article/pii/S2213231717307425Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b13897abda95ce40fb1e631f0e1a131e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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