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Cited by 3Liver Disease Diagnosis and TreatmentLipid metabolism and biosynthesisDrug-Induced Hepatotoxicity and Protection

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Investigating the process of apoptosis in HepG2 cells treated with palmitate, oleate, and palmitate/oleate combination

Torabi, Samaneh, Mohammadi, Yaser, Hoseini, Motahareh-sadat, Rezaei, Atena, Mohammadi, Ali, Bahreini, Elham·2025·Arab Journal of Gastroenterology
DOI 10.1016/j.ajg.2025.09.002
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Abstract

Introduction Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is characterized by lipid droplet (LD) accumulation in more than 5% of hepatocytes. This study aimed to investigate apoptosis in HepG2 cells exposed to palmitate, oleate, and a combination of palmitate and oleate. Methods The effective concentrations of palmitic and oleic acids were determined using the MTT assay. Subsequently, an optimal combined dose of these fatty acids was selected to induce LD formation. Intracellular LD accumulation following treatment with different concentrations of palmitate and oleate was assessed qualitatively and semi-quantitatively using Oil Red O staining and light microscopy. Expression levels of apoptosis-related genes (p53, Bax, FasL, and Bcl-2) were quantified using real-time PCR. Results Palmitate treatment markedly reduced cell density and enhanced LD accumulation, whereas oleate exhibited milder effects. The palmitate-oleate (P&O) combination induced greater LD accumulation than oleate alone but was less cytotoxic than palmitate. At the molecular level, pro-apoptotic genes (P53, Bax, and FasL) were upregulated in all treated groups, with the highest expression in the P&O group. Conversely, the anti-apoptotic gene Bcl-2 was significantly downregulated in palmitate-treated cells. Conclusion Saturated and unsaturated fatty acids exert distinct yet interconnected effects on lipid homeostasis and hepatocyte viability. Maintaining their proper balance may be critical in preventing liver injury. Further studies are warranted to elucidate the underlying mechanisms.

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References 35 · Cited by 3

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  1. Mitra S, De A, Chowdhury A (2020) Epidemiology of non-alcoholic and alcoholic fatty liver diseases. Transl Gastroenterol Hepatol 5: 16. 10.21037/tgh.2019.09.08. · DOI
  2. Lazarus, 2022, Advancing the global public health agenda for NAFLD: a consensus statement, Nat Rev Gastroenterol Hepatol, 19, 60, 10.1038/s41575-021-00523-4 · DOI · Paper page
  3. Motta, 2023, From non-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC): epidemiology, incidence, predictions, risk factors, and prevention, Cancers, 15, 10.3390/cancers15225458 · DOI
  4. Chen, 2018, Oleic acid protects saturated fatty acid mediated lipotoxicity in hepatocytes and rat of non-alcoholic steatohepatitis, Life Sci, 203, 291, 10.1016/j.lfs.2018.04.022 · DOI
  5. Zeng, 2020, Oleic acid ameliorates palmitic acid induced hepatocellular lipotoxicity by inhibition of ER stress and pyroptosis, Nutrit Metabol, 17, 11, 10.1186/s12986-020-0434-8 · DOI
  6. Cho, 2008, Involvement of endoplasmic reticulum stress in palmitate-induced apoptosis in HepG2 Cells, Toxicol Res, 24, 129, 10.5487/TR.2008.24.2.129 · DOI
  7. Yki-Järvinen, 2021, Dietary carbohydrates and fats in nonalcoholic fatty liver disease, Nat Rev Gastroenterol Hepatol, 18, 770, 10.1038/s41575-021-00472-y · DOI · Paper page
  8. Berná, 2020, The role of nutrition in non-alcoholic fatty liver disease: Pathophysiology and management, Liver Int, 40, 102, 10.1111/liv.14360 · DOI
  9. Mustafa, 2024, Apoptosis: a comprehensive overview of signaling pathways, morphological changes, and physiological significance and therapeutic implications, Cells, 13, 10.3390/cells13221838 · DOI · Paper page
  10. Li, 2025, TERT-TP53 mutations: a novel biomarker pair for hepatocellular carcinoma recurrence and prognosis, Sci Rep, 15, 3620, 10.1038/s41598-025-87545-z · DOI
  11. Saddam, 2024, Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context, Egypt J Med Human Genet, 25, 12, 10.1186/s43042-024-00485-7 · DOI
  12. Wang, 2018, The role of the Fas/FasL signaling pathway in environmental toxicant-induced testicular cell apoptosis: an update, Syst Biol Reprod Med, 64, 93, 10.1080/19396368.2017.1422046 · DOI
  13. Listenberger, 2003, Triglyceride accumulation protects against fatty acid-induced lipotoxicity, PNAS, 100, 3077, 10.1073/pnas.0630588100 · DOI · Paper page
  14. Wei, 2006, Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells, Am J Phys Endocrinol Metab, 291, E275, 10.1152/ajpendo.00644.2005 · DOI
  15. Ricchi, 2009, Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes, J Gastroenterol Hepatol, 24, 830, 10.1111/j.1440-1746.2008.05733.x · DOI
  16. Hosseini, 2025, Comparative analysis of β-Estradiol and testosterone on lipid droplet accumulation, and regulatory protein expression in palmitate/oleate-induced fatty HepG2 cells, BMC Gastroenterol, 25, 263, 10.1186/s12876-025-03863-6 · DOI
  17. Sarnyai, 2020, Effect of cis- and trans-monounsaturated fatty acids on palmitate toxicity and on palmitate-induced accumulation of ceramides and diglycerides, Int J Mol Sci, 21, 10.3390/ijms21072626 · DOI
  18. AlGhamdi, 2015, Synergistic interaction between lipid-loading and doxorubicin exposure in Huh7 hepatoma cells results in enhanced cytotoxicity and cellular oxidative stress: implications for acute and chronic care of obese cancer patients, Toxicol Res, 4, 1479, 10.1039/C5TX00173K · DOI
  19. Mei, 2011, Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes, J Pharmacol Exp Ther, 339, 487, 10.1124/jpet.111.184341 · DOI
  20. Nakshatra U, Jayaraman S, Veeraraghavan VP, Murali R (2025). Molecular mechanisms underlying the anticancer activity of chrysin through p53 tumor suppressor in HepG2 cell lines. Texila Int J Public Health. 10.21522/TIJPH.2013.SE.25.01.Art024. · DOI
  21. Wang, 2023, ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis, Arch Toxicol, 97, 1439, 10.1007/s00204-023-03476-6 · DOI
  22. Yun, 2024, Doxorubicin Attenuates Free Fatty Acid-Induced Lipid Accumulation via Stimulation of p53 in HepG2 Cells, Biomol Ther (Seoul), 32, 94, 10.4062/biomolther.2023.200 · DOI
  23. Cazanave, 2010, Mechanisms and clinical implications of hepatocyte lipoapoptosis, Clinical lipidology, 5, 71, 10.2217/clp.09.85 · DOI
  24. Cazanave, 2010, CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis, Am J Physiol Gastrointest Liver Physiol, 299, G236, 10.1152/ajpgi.00091.2010 · DOI
  25. Chota, 2021, Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death, Oncotarget, 12, 1615, 10.18632/oncotarget.28031 · DOI
  26. Malhi, 2006, Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis *, J Biol Chem, 281, 12093, 10.1074/jbc.M510660200 · DOI
  27. Korbecki, 2019, The effect of palmitic acid on inflammatory response in macrophages: an overview of molecular mechanisms, Inflammat Res, 68, 915, 10.1007/s00011-019-01273-5 · DOI
  28. Šrámek, 2021, Molecular mechanisms of apoptosis induction and its regulation by fatty acids in pancreatic β-Cells, Int J Mol Sci, 22, 10.3390/ijms22084285 · DOI
  29. Yuzefovych, 2010, Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress, Am J Physiol-Endocrinol Metab, 299, E1096, 10.1152/ajpendo.00238.2010 · DOI · Paper page
  30. Sargsyan E, Artemenko K, Manukyan L, Bergquist J, Bergsten P (2016) Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1861(9, Part A): 1151-1160. https://doi.org/10.1016/j.bbalip.2016.06.012. · DOI
  31. Mularczyk, 2021, Probiotics-rich emulsion improves insulin signalling in Palmitate/Oleate-challenged human hepatocarcinoma cells through the modulation of Fetuin-A/TLR4-JNK-NF-κB pathway, Biomed Pharmacother, 139, 10.1016/j.biopha.2021.111560 · DOI
  32. Zhang, 2010, Synergistic effect of cAMP and palmitate in promoting altered mitochondrial function and cell death in HepG2 cells, Exp Cell Res, 316, 716, 10.1016/j.yexcr.2009.12.008 · DOI
  33. Anstee, 2006, Mouse models in non-alcoholic fatty liver disease and steatohepatitis research, Int J Exp Pathol, 87, 1, 10.1111/j.0959-9673.2006.00465.x · DOI · Paper page
  34. Donato, 2008, Functional assessment of the quality of human hepatocyte preparations for cell transplantation, Cell Transplant, 17, 1211, 10.3727/096368908787236620 · DOI

Metadata

Authors
Torabi, S., Mohammadi, Y., Hoseini, M.-S., Rezaei, A., Mohammadi, A., & Bahreini, E.
Affiliations
Iran University of Medical Sciences (IR)
Corresponding author
Bahreini, Elham
ORCID
Venue
Arab Journal of Gastroenterology
Publisher
Elsevier BV
Published
2025-11
Volume
26
Issue
4
Pages
383-389
ISSN
1687-1979 (ISSN-L)
DOI
10.1016/j.ajg.2025.09.002
OpenAlex
W4415946511
Cited by
3
References
35
Citations by year
2026: 3
FWCI
2.09
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Arab Journal of Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
apoptosis, HepG2 cells, palmitate, oleate, non-alcoholic fatty liver disease, lipid droplet accumulation, saturated fatty acids, unsaturated fatty acids, p53, Bax, Fas ligand, Bcl-2, hepatocyte viability, lipid homeostasis
MeSH terms
Humans, Palmitates, Tumor Suppressor Protein p53, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Oleic Acid, Palmitic Acid, Hepatocytes, bcl-2-Associated X Protein, Fas Ligand Protein, Hep G2 Cells, Non-alcoholic Fatty Liver Disease, Lipid Droplets

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CoChat. (2026). Citation check: Investigating the process of apoptosis in HepG2 cells treated with palmitate, oleate, and palmitate/oleate combination. https://app.cochat.ai/papers/10.1016/j.ajg.2025.09.002
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Torabi, S., Mohammadi, Y., Hoseini, M.-S., Rezaei, A., Mohammadi, A., & Bahreini, E. (2025). Investigating the process of apoptosis in HepG2 cells treated with palmitate, oleate, and palmitate/oleate combination. Arab Journal of Gastroenterology. https://doi.org/10.1016/j.ajg.2025.09.002