Aquaporin-9 is involved in the lipid-lowering activity of the nutraceutical silybin on hepatocytes through modulation of autophagy and lipid droplets composition
| Autor: | Francesca Baldini, Adriana Voci, Gianluca Damonte, Patrizia Gena, Michela Bonomo, Elena Grasselli, Piero Portincasa, Nadia Serale, Marilina Florio, Laura Vergani, Giuseppe Calamita, Annalisa Salis |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Steatosis Glycerol transport Pharmacology Aquaporins medicine.disease_cause 03 medical and health sciences Aquaglyceroporins Autophagy Hepatic glycerol Mono-unsaturated and saturated fatty acids Silybin Steatohepatitis 0302 clinical medicine Cell Line Tumor Lipid droplet medicine Animals Molecular Biology Chemistry Acyl-CoA Dehydrogenase Long-Chain Fatty liver Lipid metabolism Lipid Droplets Cell Biology Lipid Metabolism medicine.disease Mitochondria Rats MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Hepatocytes Oxidative stress |
| Popis: | Hepatic steatosis is the hallmark of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome and insulin resistance with potential evolution towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Key roles of autophagy and oxidative stress in hepatic lipid accumulation and NAFLD progression are recognized. Here, we employed a rat hepatoma cell model of NAFLD progression made of FaO cells exposed to oleate/palmitate followed or not by TNFα treatment to investigate the molecular mechanisms through which silybin, a lipid-lowering nutraceutical, may improve hepatic lipid dyshomeostasis. The beneficial effect of silybin was found to involve amelioration of the fatty acids profile of lipid droplets, stimulation of the mitochondrial oxidation and upregulation of a microRNA of pivotal relevance in hepatic fat metabolism, miR-122. Silybin was also found to restore the levels of Aquaporin-9 (AQP9) and glycerol permeability while reducing the activation of the oxidative stress-dependent transcription factor NF-κB, and autophagy turnover. In conclusion, silybin was shown to have molecular effects on signaling pathways that were previously unknown and potentially protect the hepatocyte. These actions intersect TG metabolism, fat-induced autophagy and AQP9-mediated glycerol transport in hepatocytes. |
| Databáze: | OpenAIRE |
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