Excess fructose and fatty acids trigger a model of non‑alcoholic fatty liver disease progression in vitro: Protective effect of the flavonoid silybin

Grasselli,Elena; Baldini,Francesca; Vecchione,Giulia; Oliveira,Paulo   J.; Sardão,Vilma   A.; Voci,Adriana; Portincasa,Piero; Vergani,Laura

doi:10.3892/ijmm.2019.4234

Excess fructose and fatty acids trigger a model of non‑alcoholic fatty liver disease progression in vitro: Protective effect of the flavonoid silybin

Authors:
- Elena Grasselli
- Francesca Baldini
- Giulia Vecchione
- Paulo J. Oliveira
- Vilma A. Sardão
- Adriana Voci
- Piero Portincasa
- Laura Vergani
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Affiliations: DISTAV‑Department of Earth, Environment and Life Sciences, University of Genova, I‑16132 Genova, Italy, CNC‑Center for Neuroscience and Cellular Biology, University of Coimbra, 3060‑197 Cantanhede, Portugal, Division of Internal Medicine ‘A. Murri’, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, I‑70162 Bari, Italy
Published online on: June 6, 2019 https://doi.org/10.3892/ijmm.2019.4234
Pages: 705-712

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Abstract

Overconsumption of fats and sugars is a major cause of development of non‑alcoholic fatty liver disease (NAFLD). The main objectives of the present study were to explore the pathways sustaining the interfering metabolic effects of excess fructose and fatty acids in hepatocytes, and to clarify the mechanisms through which the nutraceutical silybin rescues the functional and metabolic alterations that are associated with the NALFD progression. Cultured hepatocytes were exposed to fructose and fatty acids, alone or in combination, to induce different grades of steatosis in vitro. Cell viability, apoptosis, free radical production, lipid content, lipid peroxidation and activity of lipogenic enzymes were assessed by spectrophotometric assays. Oxygen consumption and mitochondrial respiration parameters were measured using a Seahorse analyzer. Expression of markers for liver steatosis and dysfunction were also evaluated by reverse transcription‑quantitative polymerase chain reaction. The data revealed that fructose and fatty acid combination in vitro had a positive interference on lipogenic pathways, leading to more severe steatosis and liver dysfunction, reduced cell viability, increased apoptosis, oxidative stress and mitochondrial respiration. Hepatic cell abnormalities were almost completely alleviated by silybin treatment. These findings suggest that silybin may serve as a novel and cost‑effective dietary supplement for treatment and/or prevention of hepatosteatosis associated with NAFLD progression.

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