Exploratory Data Analysis of Cell and Mitochondrial High-Fat, High-Sugar Toxicity on Human HepG2 Cells
Open accessAbstract
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.
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To induce steatosis in HepG2, supraphysiological concentrations of FFAs (0.5-2.0 mM) are often used.
“Second, to induce steatosis, supraphysiological concentrations of FFAs (concentrations of 0.5–2.0 mM) are often used in HepG2 experiments [28,91,125,126,127,128,129,130].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [91]
Methods §2.3 and Results §3.1 report that the authors treated HepG2 cells with 0.5 mM palmitic acid and observed increased lipid accumulation, supporting an example at the low end of the cited range. The paper used 0.25 mM for its FFA mixture and does not establish that 0.5–2.0 mM is often used across HepG2 experiments. (LLM, conf=0.86)
Experimental — accuracy not yet measuredFructose alone does not reliably induce de novo lipogenesis or triglyceride accumulation in HepG2, even at concentrations up to 20-25 mM and incubation times from 48 h to 28 days.
“The limited reproducibility of fructose-induced DNL is a particularly significant limitation for MASLD studies, where sugar/fructose loading is considered one of the key pathogenic factors, as the ability of fructose to induce steatosis directly in HepG2 hepatoma cells remains controversial.”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [91]
Results §3.1 reports that fructose alone did not increase intracellular lipid content in HepG2 cells, supporting the concern about direct fructose-induced steatosis. But Methods §2.3 tested 10 mM fructose for only 1, 6, and 24 hours; the paper does not establish the claim for 20–25 mM or 48 hours to 28 days, nor does it directly measure de novo lipogenesis. The Discussion says longer incubations should be studied to assess triglyceride accumulation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHepG2 is suitable for primary testing of intracellular TG and lipid droplet reduction, normalization of ER stress/ROS markers, restoration of mitochondrial function in lipotoxicity, and effects on transcriptional programs.
“Thus, HepG2 is suitable for primary testing of intracellular TG and lipid droplet reduction, normalization of ER stress/ROS markers, restoration of mitochondrial function in lipotoxicity, and effects on transcriptional programs (lipogenesis, β-oxidation, inflammation) [80,91,92,93,94].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [91]
The Discussion (page not provided) calls HepG2 a suitable model for studying steatotic phenotypes and reports fatty-acid-induced lipid-droplet accumulation, increased ROS, and mitochondrial impairment. These findings support using it to assess lipid droplets, ROS, and mitochondrial function in lipotoxicity, but the paper does not establish the full proposed testing scope: intracellular TG reduction, normalization of ER-stress markers, or effects on transcriptional programs. (LLM, conf=0.86)
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Cites
Scikit-learn: Machine Learning in Python
Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Müller, A., Nothman, J., Louppe, G., et al. (2012) · arXiv · doi:10.48550/arxiv.1201.0490 · Cited by 71,016 · see citing works
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751 · cited 1× · see citing works
“Mitochondrial lipids were extracted accordingly to Bligh and Dyer method [32].”
Method(1967) · Cited by 23,719 · see citing works
Apoptosis: A Review of Programmed Cell Death
Elmore, S. (2007) · Toxicologic Pathology · doi:10.1080/01926230701320337 · Cited by 13,853 · see citing works
Data Structures for Statistical Computing in Python
McKinney, W. (2010) · Proceedings of the Python in Science Conferences · doi:10.25080/majora-92bf1922-00a · Cited by 11,511 · see citing works
The NumPy Array: A Structure for Efficient Numerical Computation
van der Walt, S., Colbert, S. C., & Varoquaux, G. P. (2011) · Computing in Science & Engineering · doi:10.1109/mcse.2011.37 · Cited by 10,444 · see citing works
Sulforhodamine B colorimetric assay for cytotoxicity screening
Vichai, V., & Kirtikara, K. (2006) · Nature Protocols · doi:10.1038/nprot.2006.179 · Cited by 3,679 · see citing works
Rouser, G., Fleischer, S., & Yamamoto, A. (1970) · Lipids · doi:10.1007/bf02531316 · Cited by 3,280 · see citing works
Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis
Anstee, Q. M., Targher, G., & Day, C. P. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.41 · Cited by 1,747 · see citing works
Mitochondrial Dynamics and Metabolic Regulation
Wai, T., & Langer, T. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.12.001 · Cited by 1,304 · see citing works
Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis
Brentnall, M., Rodriguez-Menocal, L., Guevara, R. L. D., Cepero, E., & Boise, L. (2013) · BMC Cell Biology · doi:10.1186/1471-2121-14-32 · Cited by 1,287 · see citing works
Fu, S., Yang, L., Li, P., Hofmann, O., Dicker, L. H., Hide, W. A., Lin, X., Watkins, S. M., Ivanov, A. R., & Hotamışlıgil, G. S. (2011) · Nature · doi:10.1038/nature09968 · Cited by 1,024 · see citing works
Lauber, K., Bohn, E., Kröber, S. M., Xiao, Y.-J., Blumenthal, S. G., Lindemann, R. K., Marini, P., Wiedig, C., Zobywalski, A., Baksh, S., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00422-7 · Cited by 967 · see citing works
Dagda, R. K., Cherra, S. J., Kulich, S. M., Tandon, A., Park, D., & Chu, C. T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808515200 · Cited by 954 · see citing works
Fructose and sugar: A major mediator of non-alcoholic fatty liver disease
Jensen, T., Abdelmalek, M. F., Sullivan, S. A., Nadeau, K. J., Cree‐Green, M., Roncal, C., Nakagawa, T., Kuwabara, M., Sato, Y., Kang, D., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.01.019 · Cited by 952 · see citing works
Bereiter‐Hahn, J., & Vöth, M. (1994) · Microscopy Research and Technique · doi:10.1002/jemt.1070270303 · Cited by 900 · see citing works
Mutual Information between Discrete and Continuous Data Sets
Ross, B. C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087357 · Cited by 869 · see citing works
Hybrid threshold adaptable quantum secret sharing scheme with reverse Huffman-Fibonacci-tree coding
Lai, H., Zhang, J., Luo, M., Pan, L., Pieprzyk, J., Xiao, F., & Orgun, M. A. (2016) · Scientific Reports · doi:10.1038/srep31350 · Cited by 814 · see citing works
Li, Z., Agellon, L., Allen, T., Umeda, M., Jewell, L. S., Mason, A., & Vance, D. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.03.007 · Cited by 739 · see citing works
Wei, Y., Wang, D., Topczewski, F., & Pagliassotti, M. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00644.2005 · Cited by 736 · see citing works
Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis.
Pérez-Carreras, M., Del Hoyo, P., Martín, M. A., Rubio, J. C., Martín, A., Castellano, G., Colina, F., Arenas, J., & Solis-Herruzo, J. A. (2003) · Hepatology · doi:10.1002/hep.1840380426 · Cited by 734 · see citing works
Lipid map of the mammalian cell
Gerrit van, M. E. E. R., & de Kroon, A. I. P. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.071233 · Cited by 688 · see citing works
Ricchi, M., Odoardi, M. R., Carulli, L., Anzivino, C., Ballestri, S., Pinetti, A., Fantoni, L. I., Marra, F., Bertolotti, M., Banni, S., et al. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2008.05733.x · Cited by 652 · see citing works
Apoptosis and necroptosis in the liver: a matter of life and death
Schwabe, R. F., & Luedde, T. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0065-y · Cited by 582 · see citing works
Making heads or tails of phospholipids in mitochondria
Osman, C., Voelker, D. R., & Langer, T. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201006159 · Cited by 580 · see citing works
A Human Hepatocellular in Vitro Model to Investigate Steatosis
Gómez-Lechón, M. J., Donato, M. T., Martínez-Romero, A., Jiménez, N., Castell, J. V., & O’Connor, J.-E. (2007) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2006.11.004 · Cited by 576 · see citing works
Fructose metabolism and metabolic disease
Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96702 · Cited by 561 · see citing works
Wang, D., Wei, Y., & Pagliassotti, M. J. (2005) · Endocrinology · doi:10.1210/en.2005-0570 · Cited by 529 · see citing works
Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction?
Malik, A. N., & Czajka, A. (2012) · Mitochondrion · doi:10.1016/j.mito.2012.10.011 · Cited by 499 · see citing works
Caspase Functions in Cell Death and Disease: Figure 1.Preprint
McIlwain, D. R., Berger, T., & Mak, T. W. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a026716 · Cited by 426 · see citing works
Younossi, Z. M., Marchesini, G., Cortez‐Pinto, H., & Petta, S. (2018) · Transplantation · doi:10.1097/tp.0000000000002484 · Cited by 405 · see citing works
Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes
Ly, L. D., Xu, S., Choi, S.-K., Ha, C.-M., Thoudam, T., Cha, S.-K., Wiederkehr, A., Wollheim, C. B., Lee, I.-K., & Park, K.-S. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.157 · Cited by 378 · see citing works
Kohli, R., Kirby, M., Xanthakos, S. A., Softic, S., Feldstein, A. E., Saxena, V., Tang, P., Miles, L., Miles, M. V., Balistreri, W. F., et al. (2010) · Hepatology · doi:10.1002/hep.23797 · Cited by 377 · see citing works
Tasseva, G., Bai, H. D., Davidescu, M., Haromy, A., Michelakis, E. D., & Vance, J. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.434183 · Cited by 371 · see citing works
Blue Native electrophoresis to study mitochondrial and other protein complexes
Nijtmans, L. G. J. (2002) · Methods · doi:10.1016/s1046-2023(02)00038-5 · Cited by 366 · see citing works
Role of ceramides in nonalcoholic fatty liver disease
Pagadala, M. R., Kasumov, T., McCullough, A. J., Zein, N. N., & Kirwan, J. P. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.04.005 · Cited by 306 · see citing works
Recent insights on the role of cholesterol in non-alcoholic fatty liver disease
Argüello, G., Balboa, E., Arrese, M. A., & Zanlungo, S. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.05.015 · Cited by 306 · see citing works
Yang, J., Fernández‐Galilea, M., Martínez‐Fernández, L., González‐Muniesa, P., Pérez-Chávez, A., Martínez, J. A., & Moreno-Aliaga, M. J. (2019) · Nutrients · doi:10.3390/nu11040872 · Cited by 294 · see citing works
The lysosomal-mitochondrial axis in free fatty acid–induced hepatic lipotoxicity
Li, Z.-Z., Berk, M. P., McIntyre, T. M., Gores, G. J., & Feldstein, A. E. (2008) · Hepatology · doi:10.1002/hep.22183 · Cited by 289 · see citing works
Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis
Hirsova, P., Ibrabim, S. H., Gores, G. J., & Malhi, H. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066357 · Cited by 270 · see citing works
Petrosillo, G., Ruggiero, F. M., Pistolese, M., & Paradies, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03206-9 · Cited by 223 · see citing works
Mechanisms of lysophosphatidylcholine-induced hepatocyte lipoapoptosis
Kakisaka, K., Cazanave, S. C., Fingas, C. D., Guicciardi, M. E., Bronk, S. F., Werneburg, N. W., Mott, J. L., & Gores, G. J. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00301.2011 · Cited by 222 · see citing works
Vinciguerra, M., Sgroi, A., Veyrat-Durebex, C., Rubbia-Brandt, L., Buhler, L. H., & Foti, M. (2009) · Hepatology · doi:10.1002/hep.22737 · Cited by 198 · see citing works
Differential effects of central fructose and glucose on hypothalamic malonyl–CoA and food intake
Cha, S. H., Wolfgang, M. J., Tokutake, Y., Chohnan, S., & Lane, M. D. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809255105 · Cited by 191 · see citing works
CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis
Cazanave, S. C., Elmi, N. A., Akazawa, Y., Bronk, S. F., Mott, J. L., & Gores, G. J. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00091.2010 · Cited by 190 · see citing works
Mitochondrial Dynamics in Mitochondrial Diseases
Suarez-Rivero, J. M., Paz, M. V., de la Cruz‐Ojeda, P., de la Mata, M., Cotán, D., Oropesa-Ávila, M., de Lavera, I., Álvarez-Córdoba, M., Luzón–Hidalgo, R., & Sánchez-Alcázar, J. A. (2016) · Diseases · doi:10.3390/diseases5010001 · Cited by 187 · see citing works
Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase
Shi, X., Li, J., Zou, X., Greggain, J., R⊘dkær, S. V., Færgeman, N. J., Liang, B., & Watts, J. L. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m039669 · Cited by 175 · see citing works
Chen, X., Li, L., Liu, X., Luo, R., Liao, G., Li, L., Liu, J., Cheng, J., Lu, Y., & Chen, Y. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.04.022 · Cited by 170 · see citing works
Wu, X., Zhang, L., Gurley, E. C., Studer, E. J., Shang, J., Wang, T., Wang, C., Yan, M., Jiang, Z., Hylemon, P. B., et al. (2008) · Hepatology · doi:10.1002/hep.22239 · Cited by 165 · see citing works
Sobrecases, H., Lê, K.-A., Bortolotti, M., Schneiter, P., Ith, M., Kreis, R., Boesch, C., & Tappy, L. (2010) · Diabetes & Metabolism · doi:10.1016/j.diabet.2010.03.003 · Cited by 161 · see citing works
Egnatchik, R. A., Leamy, A. K., Noguchi, Y., Shiota, M., & Young, J. D. (2014) · Metabolism · doi:10.1016/j.metabol.2013.10.009 · Cited by 161 · see citing works
Egnatchik, R. A., Leamy, A. K., Jacobson, D. A., Shiota, M., & Young, J. D. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.05.004 · Cited by 160 · see citing works
Arendt, B. M., David, W. L., Simons, B. L., Noureldin, S. A., Therapondos, G., Guindi, M. M., Sherman, M., & Allard, J. P. (2013) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2012-0261 · Cited by 154 · see citing works
Sorice, M., Circella, A., Cristea, I. M., Garofalo, T., Renzo, L. D., Alessandri, C., Valesini, G., & Esposti, M. D. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401457 · Cited by 153 · see citing works
Mitochondrial Morphology in Metabolic Diseases
Galloway, C. A., & Yoon, Y. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4779 · Cited by 141 · see citing works
Kurek, K., Ziembicka, D., Wiesiołek‐Kurek, P., Łukaszuk, B., Chabowski, A., Górski, J., & Żendzian‐Piotrowska, M. (2013) · Liver International · doi:10.1111/liv.12331 · Cited by 132 · see citing works
Sun, Q., Zhong, W. H., Zhang, W., & Zhou, Z. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00270.2015 · Cited by 116 · see citing works
van der Veen, J. N., Lingrell, S., da Silva, R. P., Jacobs, R. L., & Vance, D. E. (2014) · Diabetes · doi:10.2337/db13-0993 · Cited by 113 · see citing works
Vaughan, R. A., Garcia-Smith, R., Bisoffi, M., Conn, C. A., & Trujillo, K. A. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-142 · Cited by 112 · see citing works
Carabelli, J., Burgueño, A. L., Rosselli, M. S., Gianotti, T. F., Lago, N. R., Pirola, C. J., & Sookoian, S. C. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01128.x · Cited by 112 · see citing works
Understanding Detergent Effects on Lipid Membranes: A Model Study of Lysolipids
Henriksen, J. R., Andresen, T. L., Feldborg, L. N., Duelund, L., & Ipsen, J. H. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.01.037 · Cited by 111 · see citing works
Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver
Lehmann, R., Franken, H., Dammeier, S., Rosenbaum, L., Kantartzis, K., Peter, A., Zell, A., Adam, P., Li, J., Xu, G., et al. (2013) · Diabetes Care · doi:10.2337/dc12-1760 · Cited by 109 · see citing works
Nile Red Binding to HepG2 Cells: An Improved Assay for In Vitro Studies of Hepatosteatosis
McMillian, M., Grant, E. R., Zhong, Z., Parker, J. B., Li, L., Zivin, R. A., Burczynski, M. E., & Johnson, M. D. (2001) · In Vitro & Molecular Toxicology · doi:10.1089/109793301753407948 · Cited by 107 · see citing works
Joseph, L. C., Barca, E., Subramanyam, P., Komrowski, M., Pajvani, U., Colecraft, H. M., Hirano, M., & Morrow, J. P. (2016) · PLOS ONE · doi:10.1371/journal.pone.0145750 · Cited by 99 · see citing works
Hepatic Adverse Effects of Fructose Consumption Independent of Overweight/Obesity
Schultz, A., Neil, D., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141121873 · Cited by 99 · see citing works
Lipotoxicity in HepG2 cells triggered by free fatty acids.
(2011) · PubMed Central · Cited by 94 · see citing works
Carbohydrate intake and nonalcoholic fatty liver disease
Neuschwander‐Tetri, B. A. (2013) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328361c4d1 · Cited by 89 · see citing works
Apoptosis-induced changes in mitochondrial lipids
Crimi, M., & Esposti, M. D. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.09.014 · Cited by 86 · see citing works
Li, H., Xiao, Y., Tang, L., Zhong, F., Huang, G., Xu, J., Xu, A., Dai, R.-P., & Zhou, Z. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00081 · Cited by 80 · see citing works
Aoun, M., Fouret, G., Michel, F., Bonafos, B., Ramos, J., Cristol, J., Carbonneau, M., Coudray, C., & Feillet‐Coudray, C. (2012) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-012-9448-x · Cited by 71 · see citing works
Ferreira, D. M. S., Afonso, M. B., Rodrigues, P. M., Simão, A. L., Pereira, D. M., Borralho, P. M., Rodrigues, C. M. P., & Castro, R. E. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00420-13 · Cited by 70 · see citing works
Multiple pathways are involved in palmitic acid-induced toxicity
Park, E., Lee, A. Y., Park, S. J., Kim, J. H., & Cho, M. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.01.027 · Cited by 69 · see citing works
Kominami, K., Nakabayashi, J., Nagai, T., Tsujimura, Y., Chiba, K., Kimura, H., Miyawaki, A., Sawasaki, T., Yokota, H., MANABE, N., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.07.003 · Cited by 65 · see citing works
Zhang, Y., Dong, L., Yang, X., Shi, H., & Zhang, L. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-81 · Cited by 62 · see citing works
Pardo, V., González‐Rodríguez, Á., Guijas, C., Balsinde, J., & Valverde, Á. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.649483 · Cited by 60 · see citing works
Determination of Metabolic Viability and Cell Mass Using a Tandem Resazurin/Sulforhodamine B Assay
Silva, F. S. G., Старостина, И. Г., Ivanova, V. V., Rizvanov, A. A., Oliveira, P. J., & Pereira, S. P. (2016) · Current Protocols in Toxicology · doi:10.1002/cptx.1 · Cited by 60 · see citing works
Self-citationZhao, L., Guo, X., Wang, O., Zhang, H., Wang, Y., Zhou, F. L., Liu, J., & Ji, B. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500635 · Cited by 54 · see citing works
Mitochondrial lipid transport and biosynthesis: A complex balance
Mesmin, B. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201606069 · Cited by 54 · see citing works
Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids into the bilayer
Goonesinghe, A., MUNDY, E. S., SMITH, M., Khosravi‐Far, R., Martinou, J., & Esposti, M. D. (2005) · Biochemical Journal · doi:10.1042/bj20041389 · Cited by 52 · see citing works
Pátková, J., Anděl, M., & Trnka, J. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358709 · Cited by 44 · see citing works
Beta cell response to nutrient overload involves phospholipid remodelling and lipid peroxidation
Cohen, G., Shamni, O., Avrahami, Y., Cohen, O., Broner, E. C., Filippov-Levy, N., Chatgilialoglu, C., Ferreri, C., Kaiser, N., & Sasson, S. (2015) · Diabetologia · doi:10.1007/s00125-015-3566-z · Cited by 43 · see citing works
Wu, H., Chen, W., Cheng, K., Ku, P., Yeh, C., & Cheng, J. (2011) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.07.006 · Cited by 41 · see citing works
Busch, S. J., Barnhart, R. L., Martin, G. A., Flanagan, M. A., & Jackson, R. L. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45729-8 · Cited by 40 · see citing works
Kinase Signaling in Apoptosis Induced by Saturated Fatty Acids in Pancreatic β-Cells
Šrámek, J., Němcová‐Fürstová, V., & Kovár̆, J. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091400 · Cited by 37 · see citing works
Vecchione, G., Grasselli, E., Cioffi, F., Baldini, F., Oliveira, P. J., Sardão, V. A., Cortese, K., Lanni, A., Voci, A., Portincasa, P., et al. (2017) · Frontiers in Nutrition · doi:10.3389/fnut.2017.00042 · Cited by 37 · see citing works
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Spitz, D. R., Kinter, M. T., Kehrer, J. P., & Roberts, R. J. (1992) · Pediatric Research · doi:10.1203/00006450-199209000-00024 · Cited by 32 · see citing works
Fouret, G., Gaillet, S., Lecomte, J., Bonafos, B., Djohan, Y. F., Baréa, B., Badia, É., Coudray, C., & Feillet‐Coudray, C. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114517003713 · Cited by 31 · see citing works
Lee, M.-S., Shin, Y., Moon, S., Kim, S., & Kim, Y. (2016) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2016.21.4.317 · Cited by 31 · see citing works
Benga, G., Hodârnău, A., Böhm, B., Borza, V., Tilinca, R., Dancea, S., Petrescu, I., & FERDINAND, W. (1978) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1978.tb12205.x · Cited by 29 · see citing works
9-PAHSA Prevents Mitochondrial Dysfunction and Increases the Viability of Steatotic Hepatocytes
Moreira, A. R. S., Rüschenbaum, S., Schefczyk, S., Hendgen-Cotta, U. B., Rassaf, T., Broering, R., Hardtke‐Wolenski, M., & Buitrago‐Molina, L. E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218279 · Cited by 26 · see citing works
Meissen, J. K., Hirahatake, K. M., Adams, S. H., & Fiehn, O. (2014) · Metabolomics · doi:10.1007/s11306-014-0729-8 · Cited by 22 · see citing works
Swapna Sasi, U. S., Sindhu, G., & Raghu, K. G. (2020) · Toxicology in Vitro · doi:10.1016/j.tiv.2020.104952 · Cited by 19 · see citing works
Agoun, H., Semiane, N., Mallek, A., Bellahreche, Z., Hammadi, S., Madjerab, M., Abdlalli, M., Khalkhal, A., & Dahmani, Y. (2021) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2019.1621350 · Cited by 15 · see citing works
Einer, C., Hohenester, S. D., Wimmer, R., Wottke, L., Artmann, R., Schulz, S., Gosmann, C., Simmons, A., Leitzinger, C., Eberhagen, C., et al. (2017) · Data in Brief · doi:10.1016/j.dib.2017.09.019 · Cited by 11 · see citing works
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Kučera, O., Lotková, H., Sobotka, O., & Červinková, Z. (2015) · Physiological Research · doi:10.33549/physiolres.933225 · Cited by 8 · see citing works
Flagged first, then by citations
5 of the 100 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [16]Zhang K. Chang Y. Shi Z. Han X. Han Y. Yao Q. Hu Z. Cui H. Zheng L. Han T. ω-3 PUFAs ameliorate liver fibrosis and inhibit hepatic stellate cells proliferation and acti-vation by promoting YAP/TAZ degradation Sci. Rep. 2016 6 1 14 27435808 PMC4951777
- [68]García-Ruiz I. Solís-Muñoz P. Fernández-Moreira D. Muñoz-Yagüe T. Solís-Herruzo J.A. In vitro treatment of HepG2 cells with saturated fatty acids reproduces mitochondrial dysfunction found in nonalcoholic steatohepatitis DMM Dis. Model Mech. 2015 8 183 191 25540128 PMC4314783
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Younis, F. A., Saleh, S. R., El‐Rahman, S. S. A., Newairy, A. A., Demellawy, M. E., & Ghareeb, D. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-21568-8 · Cited by 64 · see citing works
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Self-citationMaseko, T., Elkalaf, M., Peterová, E., Lotková, H., Staňková, P., Melek, J., Dušek, J., Žádníková, P., Čížková, D., Bezrouk, A., et al. (2023) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2023.5342 · Cited by 21 · see citing works
Ondee, T., Pongpirul, K., Udompornpitak, K., Sukkummee, W., Lertmongkolaksorn, T., Senaprom, S., & Leelahavanichkul, A. (2023) · Nutrients · doi:10.3390/nu15061462 · Cited by 14 · see citing works
Saleh, S. R., Younis, F. A., Abdelrahman, S. S. M., Attia, A. A., Demellawy, M. E., Newairy, A. A., & Ghareeb, D. A. (2024) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-024-00695-6 · Cited by 9 · see citing works
Khatoon, S., Das, N., Chattopadhyay, S., Joharapurkar, A. A., Singh, A., Patel, V. J., Nirwan, A., Kumar, A., Mugale, M. N., Mishra, D. P., et al. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176800 · Cited by 8 · see citing works
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Castelão-Baptista, J. P., Valente, S. A., Canário, S., Oppolzer, D., Barros, A., Venâncio, C., Martins, T., Antunes, L., Sardão, V. A., Rosa, E., et al. (2023) · Nutrients · doi:10.3390/nu15040924 · Cited by 5 · see citing works
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Self-citationYudhani, R. D., Nugrahaningsih, D. A. A., Sholikhah, E. N., & Mustofa, M. (2023) · AIP conference proceedings · doi:10.1063/5.0111536
Zhou, Y., Han, Y. Y., & Shu, Q. (2024) · Research Square · doi:10.21203/rs.3.rs-4957397/v1
Li, Y., Liu, F., Huang, Y., Chang, S. K., Niu, C., Liu, P., Li, X., Yao, L., & Qiu, S. (2026) · Journal of Future Foods · doi:10.1016/j.jfutfo.2026.03.004
- Authors
- Amorim, R., Simões, I., Veloso, C., Carvalho, A., Simões, R., Pereira, F., Thiel, T., Normann, A., Morais, C., Jurado, A., Wieckowski, M., Teixeira, J., & Oliveira, P.
- Affiliations
- Universidade do Porto (PT)
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Biocant – Associação de Transferência de Tecnologia (PT)
- Universidade Politécnica de Coimbra (PT)
- Mediagnostic, D-72770 Reutlingen, Germany
- Centro de Neurociências e Biologia Celular (PT)
- Corresponding author
- Oliveira, Paulo
- ORCID
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2021-05-19
- Volume
- 13
- Issue
- 5
- Pages
- 1723
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC8161147
- OpenAlex
- W3161921875
- Cited by
- 21
- References
- 100
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 1
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Estudo Geral (Universidad de Coimbra) (submittedVersion, cc-by)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
- Funders
- Fundação para a Ciência e Tecnologia (FCT) (PTDC/BTM-SAL/29297/2017, POCI-01-0145-FEDER-029297, PTDC/DTP-FTO/2433/2014, POCI-01-0145-FEDER-016659, PTDC/BIA-MOL/28607/2017, POCI-01-0145-FEDER-028607, POCI-01-0145-FEDER-006980, NORTE-01-0145-FEDER-000028, PTDC/ASP-HOR/29152/2017, POCI-01-0145-FEDER-0)
- H2020 Marie Skłodowska-Curie Actions (722619, 734719)
- Narodowe Centrum Nauki (UMO-2018/29/B/NZ1/00589)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, HepG2 cells, palmitic acid, free fatty acids, fructose, mitochondrial dysfunction, reactive oxygen species, lipid accumulation, mitochondrial membrane potential, mitochondrial morphology, oxygen consumption, caspase activation, cell death, fructokinase, mitochondrial phospholipids, high-fat high-sugar diet, cell viability, unsupervised learning, high-throughput screening
- MeSH terms
- Sugars, Data Analysis, Dietary Carbohydrates, Fatty Acids, Fatty Acids, Nonesterified, Fructose, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Mitochondria, Cell Death, Reactive Oxygen Species, Oxidative Stress, Palmitic Acid, Hepatocytes, Lipid Metabolism, Hep G2 Cells, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
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