Exploring Dynamic Metabolome of the HepG2 Cell Line: Rise and Fall

Kiseleva, Olga I.; Kurbatov, Ilya; Arzumanian, Viktoriia A.; Ilgisonis, Ekaterina V.; Вахрушев, И. В.; Lupatov, A. Yu.; Ponomarenko, Elena A.; Poverennaya, Ekaterina V.

doi:10.3390/cells11223548

Cited by 7 publications

(8 citation statements)

References 47 publications

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“…Despite having similar genetic backgrounds, different examples of HepG2 cells (genetically modified or treated with various drugs and toxic agents) can display vastly different metabolic phenotypes [ 25 , 26 , 27 ]. Utilizing this variability could provide insights into the abnormal tumor metabolism and machinery of hepatocytes.…”

Section: Resultsmentioning

confidence: 99%

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The Expectation and Reality of the HepG2 Core Metabolic Profile

et al. 2023

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To represent the composition of small molecules circulating in HepG2 cells and the formation of the “core” of characteristic metabolites that often attract researchers’ attention, we conducted a meta-analysis of 56 datasets obtained through metabolomic profiling via mass spectrometry and NMR. We highlighted the 288 most commonly studied compounds of diverse chemical nature and analyzed metabolic processes involving these small molecules. Building a complete map of the metabolome of a cell, which encompasses the diversity of possible impacts on it, is a severe challenge for the scientific community, which is faced not only with natural limitations of experimental technologies, but also with the absence of transparent and widely accepted standards for processing and presenting the obtained metabolomic data. Formulating our research design, we aimed to reveal metabolites crucial to the Hepg2 cell line, regardless of all chemical and/or physical impact factors. Unfortunately, the existing paradigm of data policy leads to a streetlight effect. When analyzing and reporting only target metabolites of interest, the community ignores the changes in the metabolomic landscape that hide many molecular secrets.

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Section: Resultsmentioning

confidence: 99%

“…Nine datasets described situations in which cells were not subjected to explicit chemical or physical stimuli [ 21 , 22 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The article by Chun-Yun Zhang et al [ 31 ] is particularly interesting.…”

Section: Resultsmentioning

confidence: 99%

The Expectation and Reality of the HepG2 Core Metabolic Profile

et al. 2023

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“…The smooth endoplasmic reticulum, mitochondrial number, amino acid, and cytochrome P450 levels of HepG2 cells are lower than normal liver cells. However, it is believed that the HepG2 cells retain a complete metabolic pathway, which is considered suitable for studying the cellular mechanism of liver lipid metabolism 36 . Our experiments used oleic acid to induce lipid accumulation in HepG2 cells before adding various concentrations of gypenoside XIII.…”

Section: Discussionmentioning

confidence: 99%

“…However, it is believed that the HepG2 cells retain a complete metabolic pathway, which is considered suitable for studying the cellular mechanism of liver lipid metabolism. 36 Our experiments used oleic acid to induce lipid accumulation in HepG2 cells before adding various concentrations of gypenoside XIII. We found that gypenoside XIII improves triglyceride breakdown and contributes to reducing lipid accumulation in fatty liver cells.…”

Section: Effect Of Gypenoside XIII On Liver Inflammation In Mcd Diet-...mentioning

confidence: 99%

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice

Cheng,

Liou,

et al. 2024

The Kaohsiung J of Med Scie

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Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non‐alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline‐deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl‐CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element‐binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β‐oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.

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“…However, the lines were divided into two clusters at the transcript level: non-hepatic cell lines were grouped into one cluster and hepatic cells into another. Moreover, it can be assumed that the differences at the proteomic and metabolic levels will be more pronounced, especially given the differences observed between the passages of the HepG2 cell line [23].…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomic Analysis of Three Common Liver Cell Lines

Arzumanian

Pyatnitskiy

Poverennaya

2023

IJMS

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Background: Comparative transcriptomic analysis is a powerful approach for investigating the molecular mechanisms underlying various physiological and pathological processes, including liver disease. The liver is a vital organ with diverse functions, including metabolism and detoxification. In vitro models of liver cells, such as HepG2, Huh7, and Hep3B, have been widely used to study liver biology and pathology. However, there is limited information on the heterogeneity of these cell lines at the transcriptomic level. Objective: This study aimed to conduct a comparative transcriptomic analysis of three common liver cell lines (HepG2, Huh7, and Hep3B) using publicly available RNA-sequencing data. In addition, we compared these cell lines to primary hepatocytes, cells isolated directly from liver tissue and considered the gold standard for studying liver function and disease. Methods: Our study included sequencing data with the following criteria: total number of reads over 20,000,000, average read length of over 60 base pairs, Illumina sequencing, and non-treated cells. The data for the three cell lines were compiled: HepG2 (97 samples), Huh7 (39 samples), and Hep3B (16 samples). We performed differential gene expression analysis using the DESeq2 package, principal component analysis, hierarchical clustering on principal components, and correlation analysis to explore the heterogeneity within each cell line. Results: We identified numerous genes and pathways differentially expressed between HepG2, Huh7, and Hep3B, such as oxidative phosphorylation, cholesterol metabolism, and DNA damage. We report that the expression levels of important genes differ significantly between primary hepatocytes and liver cell lines. Conclusion: Our study provides new insights into the transcriptional heterogeneity of commonly used liver cell lines and highlights the importance of considering specific cell line. Consequently, transferring results without considering the heterogeneity of cell lines is impractical and may lead to inaccurate or distorted conclusions.

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Exploring Dynamic Metabolome of the HepG2 Cell Line: Rise and Fall

Cited by 7 publications

References 47 publications

The Expectation and Reality of the HepG2 Core Metabolic Profile

The Expectation and Reality of the HepG2 Core Metabolic Profile

Gypenoside XIII regulates lipid metabolism in HepG2 hepatocytes and ameliorates nonalcoholic steatohepatitis in mice

Comparative Transcriptomic Analysis of Three Common Liver Cell Lines

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