Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells
| Autor: | Andrea Normann, Ines C.M. Simoes, Paulo J. Oliveira, Theresa Thiel, Catarina M. Morais, Caroline D. Veloso, Ricardo Amorim, Rui F. Simões, José A. Teixeira, Adriana Bastos Carvalho, Mariusz R. Wieckowski, Francisco B. Pereira, Amália S. Jurado |
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| Rok vydání: | 2021 |
| Předmět: |
Data Analysis
0301 basic medicine Palmitic Acid Fatty Acids Nonesterified medicine.disease_cause chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease TX341-641 chemistry.chemical_classification Nutrition and Dietetics Cell Death lipid accumulation Fatty Acids Liver Neoplasms Fatty liver exploratory data analysis Hep G2 Cells Mitochondria Liver Biochemistry Intracellular non-alcoholic fatty liver disease (NAFLD) Carcinoma Hepatocellular 030209 endocrinology & metabolism Fructose Oxidative phosphorylation mitochondria dys(function) Diet High-Fat Article 03 medical and health sciences Dietary Carbohydrates medicine Humans Reactive oxygen species Nutrition. Foods and food supply Hepg2 cells Lipid metabolism Lipid Metabolism medicine.disease in vitro cell model Oxidative Stress 030104 developmental biology chemistry Hepatocytes Steatohepatitis Reactive Oxygen Species Sugars Oxidative stress Food Science |
| Zdroj: | Nutrients Volume 13 Issue 5 Pages: 1723 Nutrients, Vol 13, Iss 1723, p 1723 (2021) |
| ISSN: | 2072-6643 |
| DOI: | 10.3390/nu13051723 |
| Popis: | Non-alcoholic steatohepatitis (NASH), one of the deleterious stages of non-alcoholic fatty liver disease, remains a significant cause of liver-related morbidity and mortality worldwide. In the current work, we used an exploratory data analysis to investigate time-dependent cellular and mitochondrial effects of different supra-physiological fatty acids (FA) overload strategies, in the presence or absence of fructose (F), on human hepatoma-derived HepG2 cells. We measured intracellular neutral lipid content and reactive oxygen species (ROS) levels, mitochondrial respiration and morphology, and caspases activity and cell death. FA-treatments induced a time-dependent increase in neutral lipid content, which was paralleled by an increase in ROS. Fructose, by itself, did not increase intracellular lipid content nor aggravated the effects of palmitic acid (PA) or free fatty acids mixture (FFA), although it led to an up-expression of hepatic fructokinase. Instead, F decreased mitochondrial phospholipid content, as well as OXPHOS subunits levels. Increased lipid accumulation and ROS in FA-treatments preceded mitochondrial dysfunction, comprising altered mitochondrial membrane potential (ΔΨm) and morphology, and decreased oxygen consumption rates, especially with PA. Consequently, supra-physiological PA alone or combined with F prompted the activation of caspase pathways leading to a time-dependent decrease in cell viability. Exploratory data analysis methods support this conclusion by clearly identifying the effects of FA treatments. In fact, unsupervised learning algorithms created homogeneous and cohesive clusters, with a clear separation between PA and FFA treated samples to identify a minimal subset of critical mitochondrial markers in order to attain a feasible model to predict cell death in NAFLD or for high throughput screening of possible therapeutic agents, with particular focus in measuring mitochondrial function. |
| Databáze: | OpenAIRE |
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