ArticlePloS one2019
Hyperglycemia induces key genetic and phenotypic changes in human liver epithelial HepG2 cells which parallel the Leprdb/J mouse model of non-alcoholic fatty liver disease (NAFLD).
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Effects of a Chemically Characterised Multi-Component Nutraceutical Formulation on Intestinal, Hepatic and Skeletal Muscle Responses in an In Vitro Gut-Liver-Muscle Model.International journal of molecular sciences · 2026Article
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Association between serum vitamin D concentration and liver fibrosis in diabetes mellitus patients: a cross-sectional study from the NHANES database.Acta diabetologica · 2024Article
- Label-free fluorescence turn-on detection of alkaline phosphatase activity using the calcein-CeAnalytical and bioanalytical chemistry · 2024Article
- Quantitative proteomics analysis based on data-independent acquisition reveals the effect of Shenling Baizhu powder (SLP) on protein expression in MAFLD rat liver tissue.Clinical proteomics · 2023Article
- Hepatoprotective effects of gentisic acid through its anti-oxidant properties in nicotinamide-streptozotocin induced diabetic mice.Iranian journal of basic medical sciences · 2023Article
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Excessive gluconeogenesis causes the hepatic insulin resistance paradox and its sequelae.Heliyon · 2022Review
- Mechanism of action ofSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Determining the temporal, dose, and composition effects of nutritional substrates in an in vitro model of intrahepatocellular triglyceride accumulation.Physiological reports · 2022Article
- When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD.Journal of clinical medicine · 2022Review
- As We Drink and Breathe: Adverse Health Effects of Microcystins and Other Harmful Algal Bloom Toxins in the Liver, Gut, Lungs and Beyond.Life (Basel, Switzerland) · 2022Review
- A Strategy for Screening the Lipid-Lowering Components inJournal of analytical methods in chemistry · 2022Article
- Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in the Liver, Kidney and Adipose Tissue of Hereditary Hypertriglyceridemic Rats: Possible Contribution of Attenuation of Cell Senescence and Oxidative Stress.International journal of molecular sciences · 2021 · on this mapArticle
- TNAP: A New Multitask Enzyme in Energy Metabolism.International journal of molecular sciences · 2021Review
- CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis.Biomedicines · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern. With a propensity to progress towards non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, NAFLD is an important link amongst a multitude of comorbidities including obesity, diabetes, and cardiovascular and kidney disease. As several in vivo models of hyperglycemia and NAFLD are employed to investigate the pathophysiology of this disease process, we aimed to characterize an in vitro model of hyperglycemia that was amenable to address molecular mechanisms and therapeutic targets at the cellular level. Utilizing hyperglycemic cell culturing conditions, we induced steatosis within a human hepatocyte cell line (HepG2 cells), as confirmed by electron microscopy. The deposition and accumulation of lipids within hyperglycemic HepG2 cells is significantly greater than in normoglycemic cells, as visualized and quantified by Nile red staining. Alanine aminotransferase (ALT) and alkaline phosphatase (ALP), diagnostic biomarkers for liver damage and disease, were found to be upregulated in hyperglycemic HepG2 cells as compared with normoglycemic cells. Suppression of CEACAM1, GLUT2, and PON1, and elevation of CD36, PCK1, and G6PK were also found to be characteristic in hyperglycemic HepG2 cells compared with normoglycemic cells, suggesting insulin resistance and NAFLD. These in vitro findings mirror the characteristic genetic and phenotypic profile seen in Leprdb/J mice, a well-established in vivo model of NAFLD. In conclusion, we characterize an in vitro model displaying several key genetic and phenotypic characteristics in common with NAFLD that may assist future studies in addressing the molecular mechanisms and therapeutic targets to combat this disease.
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