Saturated free fatty acids induce cholangiocyte lipoapoptosis
Open accessAbstract
UNLABELLED: Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fatty acids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation of the proapoptotic BH3-containing protein, PUMA. In addition, palmitate-induced cholangiocyte lipoapoptosis involved a time-dependent increase in the nuclear localization of forkhead family of transcription factor 3 (FoxO3). We show evidence for posttranslational modification of FoxO3, including early (6 hours) deacetylation and dephosphorylation that coincide with localization of FoxO3 in the nuclear compartment. By 16 hours, nuclear FoxO3 is both phosphorylated and acetylated. Knockdown studies confirmed that FoxO3 and its downstream target, PUMA, were critical for palmitate- and stearate-induced cholangiocyte lipoapoptosis. Interestingly, cultured cholangiocyte-derived cells did not accumulate appreciable amounts of neutral lipid upon FFA treatment. CONCLUSION: Our data show that the saturated FFAs palmitate and stearate induced cholangiocyte lipoapoptosis by way of caspase activation, nuclear translocation of FoxO3, and increased proapoptotic PUMA expression. These results suggest that cholangiocyte injury may occur through lipoapoptosis in NAFLD and nonalcoholic steatohepatitis patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cholangiocytes can undergo lipoapoptosis and senescence when exposed to increased saturated fatty acids, releasing DAMPs, SASP factors such as CCL2, and SPP1 that activate HSCs and generate fibrosis.
“Like hepatocytes, cholangiocytes can undergo lipoapoptosis and senescence in the presence of increased saturated fatty acids, which may provoke release of damage-associated molecular patterns, senescence-associated secretory patterns (such as chemokine ligand 2 (CCL2)), and SPP1, which activate HSCs to generate fibrosis (37-40).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [39]
Fatty acid-induced lipotoxicity results in cellular stress of hepatocytes, cholangiocytes and HSCs.
“Fatty acid (FA)-induced lipotoxicity results in cellular stress of hepatocytes,11 but also cholangiocytes25 and HSCs.26”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [25]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Ferreira, D. M. S., Castro, R. E., Machado, M. V., Evangelista, T., Silvestre, A. R., Costa, A., Coutinho, J. R. H., Carepa, F., Cortez‐Pinto, H., & Rodrigues, C. M. P. (2011) · Diabetologia · doi:10.1007/s00125-011-2130-8 · Cited by 97 · see citing works
RetractedOxyl radicals, redox-sensitive signalling cascades and antioxidants
Genestra, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.04.009 · Cited by 4,930 · see citing works
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239 · see citing works
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075 · see citing works
miR-34a repression of SIRT1 regulates apoptosis
Yamakuchi, M., Ferlito, M., & Lowenstein, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801613105 · Cited by 1,344 · see citing works
Mofrad, P., Contos, M., Haque, M., Sargeant, C. C., Fisher, R., Luketic, V., Sterling, R., Shiffman, M., Stravitz, R., & Sanyal, A. (2003) · Hepatology · doi:10.1053/jhep.2003.50229 · Cited by 1,221 · see citing works
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077 · see citing works
Yamaguchi, K., Yang, L., McCall, S. J., Huang, J., Yu, X. X., Pandey, S., Bhanot, S., Monia, B. P., Li, Y.-X., & Diehl, A. M. (2007) · Hepatology · doi:10.1002/hep.21655 · Cited by 1,019 · see citing works
Free Fatty Acids Induce JNK-dependent Hepatocyte Lipoapoptosis
Malhi, H., Bronk, S. F., Werneburg, N. W., & Gores, G. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m510660200 · Cited by 724 · see citing works
ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation
Yang, J.-Y., Zong, C. S., Xia, W., Yamaguchi, H., Ding, Q., Xie, X., Lang, J.-Y., Lai, C., Chang, C. J., Huang, W., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1676 · Cited by 698 · see citing works
Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease
Malhi, H., & Gores, G. J. (2008) · Seminars in Liver Disease · doi:10.1055/s-0028-1091980 · Cited by 539 · see citing works
Wang, H., Sreenivasan, U., Hu, H., Saladino, A. J., Polster, B. M., Lund, L. M., Gong, D., Stanley, W. C., & Sztalryd, C. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m017939 · Cited by 486 · see citing works
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal
You, H., Pellegrini, M., Tsuchihara, K., Yamamoto, K., Häcker, G. A., Erlacher, M., Villunger, A., & Mak, T. W. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060353 · Cited by 413 · see citing works
PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes
Schadinger, S. E., Bucher, N. L. R., Schreiber, B. M., & Farmer, S. R. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00513.2004 · Cited by 376 · see citing works
Lee, J., Song, M., Song, E., Kim, E., Moon, W. S., Han, M., Park, J., Kwon, K., & Park, B. (2008) · Diabetes · doi:10.2337/db07-1795 · Cited by 345 · see citing works
Ni, Y. G., Wang, N., Cao, D. J., Sachan, N., Morris, D. J., Gerard, R. D., Kuro‐o, M., Rothermel, B. A., & Hill, J. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610290104 · Cited by 278 · see citing works
Cell-free activation of a DNA-binding protein by epidermal growth factor
Sadowski, H. B., & Gilman, M. Z. (1993) · Nature · doi:10.1038/362079a0 · Cited by 258 · see citing works
Banales, J. M., Sáez, E., Úriz, M., Sarvide, S., Urribarri, A. D., Splinter, P., Tietz Bogert, P. S., Bujanda, L., Prieto, J., Medina, J. F., et al. (2012) · Hepatology · doi:10.1002/hep.25691 · Cited by 250 · see citing works
Mitogen-activated protein kinases, Erk and p38, phosphorylate and regulate Foxo1
Asada, S., Daitoku, H., Matsuzaki, H., Saito, T., SUDO, T., Mukai, H., Iwashita, S., Kako, K., Kishi, T., Kasuya, Y., et al. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.08.015 · Cited by 246 · see citing works
Bechmann, L. P., Kocabayoglu, P., Sowa, J., Sydor, S., Best, J., Schlattjan, M., Beilfuss, A., Schmitt, J., Hannivoort, R. A., Kılıçarslan, A., et al. (2013) · Hepatology · doi:10.1002/hep.26225 · Cited by 235 · see citing works
Deficiency of liver adipose triglyceride lipase in mice causes progressive hepatic steatosis
Wu, J. W., Wang, S. P., Álvarez, F., Casavant, S., Gauthier, N., Abed, L., Soni, K. G., Yang, G., & Mitchell, G. A. (2011) · Hepatology · doi:10.1002/hep.24338 · Cited by 234 · see citing works
Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation
Wang, F. S., Chan, C., Chen, K., Guan, X., Lin, H.-K., & Tong, Q. (2011) · Oncogene · doi:10.1038/onc.2011.347 · Cited by 230 · see citing works
Ohori, M., Kinoshita, T., Okubo, M., Sato, K., Yamazaki, A., Arakawa, H., Nishimura, S., Inamura, N., Nakajima, H., Neya, M., et al. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.082 · Cited by 229 · see citing works
Mechanisms of Lipotoxicity in NAFLD and Clinical Implications
Ibrahim, S. H., Kohli, R., & Gores, G. J. (2011) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31822578db · Cited by 199 · see citing works
JNK1-dependent PUMA Expression Contributes to Hepatocyte Lipoapoptosis
Cazanave, S. C., Mott, J. L., Elmi, N. A., Bronk, S. F., Werneburg, N. W., Akazawa, Y., Kahraman, A., Garrison, S. P., Zambetti, G. P., Charlton, M., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022491 · Cited by 191 · see citing works
Self-citationTranscriptional Regulation of Bim by FoxO3A Mediates Hepatocyte Lipoapoptosis
Barreyro, F. J., Kobayashi, S., Bronk, S. F., Werneburg, N. W., Malhi, H., & Gores, G. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704391200 · Cited by 188 · see citing works
MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by down-regulating Sirt1
Zhu, H., Yang, Y., Wang, Y., Li, J., Schiller, P. W., & Peng, T. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr145 · Cited by 187 · see citing works
Nutritional and Metabolic Considerations in the Etiology of Nonalcoholic Steatohepatitis
Nehra, V., Angulo, P., Buchman, A. L., & Lindor, K. D. (2001) · Digestive Diseases and Sciences · doi:10.1023/a:1012338828418 · Cited by 153 · see citing works
Natarajan, S. K., Zhu, W., Liang, X., Zhang, L., Demers, A., Zimmerman, M. C., Simpson, M. A., & Becker, D. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.07.002 · Cited by 148 · see citing works
Self-citationYuan, H., Zhang, X., Huang, X., Lu, Y., Tang, W., Man, Y., Wang, S., Xi, J., & Li, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015726 · Cited by 145 · see citing works
Masyuk, A. I., Huang, B. Q., Radtke, B. N., Gajdos, G. B., Splinter, P. L., Masyuk, T. V., Gradilone, S. A., & LaRusso, N. F. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00383.2012 · Cited by 143 · see citing works
Ho, K.-K., McGuire, V. A., Koo, C.-Y., Muir, K., de Olano, N., Maifoshie, E., Kelly, D. J., McGovern, U., Monteiro, L. J., Gomes, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.284224 · Cited by 142 · see citing works
Death Receptor 5 Signaling Promotes Hepatocyte Lipoapoptosis
Cazanave, S. C., Mott, J. L., Bronk, S. F., Werneburg, N. W., Fingas, C. D., Meng, X. W., Finnberg, N. K., El‐Deiry, W. S., Kaufmann, S. H., & Gores, G. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.280420 · Cited by 133 · see citing works
Self-citationBcl-2 is overexpressed and alters the threshold for apoptosis in a cholangiocarcinoma cell line
Harnois, D. M., Que, F. G., Celli, A., LaRusso, N. F., & Gores, G. J. (1997) · Hepatology · doi:10.1002/hep.510260413 · Cited by 130 · see citing works
Yang, Y., Zhao, Y., Liao, W., Yang, J. H., Wu, L., Zheng, Z., Yu, Y., Zhou, W., Li, L., Feng, J., et al. (2009) · Neoplasia · doi:10.1593/neo.81358 · Cited by 114 · see citing works
Histologic Spectrum of Nonalcoholic Fatty Liver Disease in Morbidly Obese Adolescents
Xanthakos, S. A., Miles, L., Bucuvalas, J. C., Daniels, S. R., García, V., & Inge, T. H. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(05)00978-x · Cited by 110 · see citing works
Sirica, A. E., Zhang, Z., Lai, G., Asano, T., Shen, X., Ward, D. J., Mahatme, A., & DeWitt, J. L. (2007) · Hepatology · doi:10.1002/hep.22088 · Cited by 84 · see citing works
Huang, L., Ramirez, J. C., Frampton, G. A., Golden, L. E., Quinn, M. A., Pae, H. Y., Horvat, D., Liang, L.-J., & DeMorrow, S. (2011) · Laboratory Investigation · doi:10.1038/labinvest.2011.62 · Cited by 83 · see citing works
Non-canonical Hedgehog signaling contributes to chemotaxis in cholangiocarcinoma
Razumilava, N., Gradilone, S. A., Smoot, R. L., Mertens, J. C., Bronk, S. F., Sirica, A. E., & Gores, G. J. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.11.005 · Cited by 83 · see citing works
Myc and PI3K/AKT signaling cooperatively repress FOXO3a-dependent PUMA and GADD45a gene expression
Amente, S., Zhang, J., Lavadera, M. L., Lania, L., Avvedimento, E. V., & Majello, B. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr638 · Cited by 79 · see citing works
The histologic spectrum of nonalcoholic fatty liver disease
Contos, M. J., Choudhury, J., Mills, A. S., & Sanyal, A. J. (2004) · Clinics in Liver Disease · doi:10.1016/j.cld.2004.04.013 · Cited by 71 · see citing works
Activation of SIRT1 protects pancreatic β-cells against palmitate-induced dysfunction
Wu, L., Zhou, L., Lü, Y., Zhang, J., Jian, F., Liu, Y., Li, F., Li, W., Wang, X. Q., & Guo, L. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.08.009 · Cited by 61 · see citing works
Becker, D., & Natarajan (2012) · Cell Health and Cytoskeleton · doi:10.2147/chc.s4955 · Cited by 60 · see citing works
A Clinical–Morphological Study on Cholestatic Presentation of Nonalcoholic Fatty Liver Disease
Sorrentino, P., Tarantino, G., Perrella, A., Micheli, P., Perrella, O., & Conca, P. (2005) · Digestive Diseases and Sciences · doi:10.1007/s10620-005-2719-1 · Cited by 55 · see citing works
Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity
Miller, T., Yang, F., Wise, C., Meng, F., Priester, S., Munshi, M. K., Guerrier, M., Dostal, D. E., & Glaser, S. S. (2011) · Digestive and Liver Disease · doi:10.1016/j.dld.2011.01.010 · Cited by 54 · see citing works
Chiba, M., Sasaki, M., Kitamura, S., Ikeda, H., Sato, Y., & Nakanuma, Y. (2011) · Journal of Clinical Pathology · doi:10.1136/jcp.2011.090175 · Cited by 43 · see citing works
Němcová‐Fürstová, V., Balušíková, K., Šrámek, J., James, R. F. L., & Kovár̆, J. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000343367 · Cited by 36 · see citing works
Harada, K., Chiba, M., Okamura, A., Hsu, M., Sato, Y., Igarashi, S., Ren, X. S., Ikeda, H., Ohta, H., Kasashima, S., et al. (2011) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2011-200040 · Cited by 30 · see citing works
Humphreys, E. H., Williams, K. T., Adams, D., & Afford, S. C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014037 · Cited by 28 · see citing works
Ginsenoside Rg3 Suppresses Palmitate-Induced Apoptosis in MIN6N8 Pancreatic β-Cells
Kim, K., Park, M. S., & Kim, H. Y. (2009) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.09-49 · Cited by 23 · see citing works
Degradation of cIAPs contributes to hepatocyte lipoapoptosis
Akazawa, Y., Guicciardi, M. E., Cazanave, S. C., Bronk, S. F., Werneburg, N. W., Kakisaka, K., Nakao, K., & Gores, G. J. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00111.2013 · Cited by 18 · see citing works
Self-citationKido, O., Fukushima, K., Ueno, Y., Inoue, J., Jefferson, D. M., & Shimosegawa, T. (2009) · Laboratory Investigation · doi:10.1038/labinvest.2009.105 · Cited by 7 · see citing works
Red oil A5 inhibits proliferation and induces apoptosis in pancreatic cancer cells
Dong, M.-L., Ding, X., & Adrian, T. E. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i1.105 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Novel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204 · see citing works
Álvarez‐Sola, G., Uriarte, I., Latasa, M. U., Fernández‐Barrena, M. G., Urtasun, R., Elizalde, M., Bárcena‐Varela, M., Jiménez, M., Chang, H. C. Y., Barbero, R., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-312975 · Cited by 164 · see citing works
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
Autophagy: a new target for nonalcoholic fatty liver disease therapy
Mao, Y., Yu, F., Wang, J., Guo, C., & Fan, X. (2016) · Hepatic Medicine Evidence and Research · doi:10.2147/hmer.s98120 · Cited by 99 · see citing works
Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD)
Iturbe-Rey, S., Maccali, C., Arrese, M. A., Aspichueta, P., de Oliveira, C. P. M. S., Castro, R. E., Lapitz, A., Izquierdo‐Sánchez, L., Bujanda, L., Perugorria, M. J., et al. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.119053 · Cited by 97 · see citing works
Leti, F., Malenica, I., Doshi, M., Courtright-Lim, A., Keuren‐Jensen, K. R. V., Legendre, C., Still, C. D., Gerhard, G. S., & DiStefano, J. K. (2015) · Translational research · doi:10.1016/j.trsl.2015.04.014 · Cited by 81 · see citing works
Radun, R., & Trauner, M. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1731707 · Cited by 81 · see citing works
To die or not to die: death signaling in nonalcoholic fatty liver disease
Akazawa, Y., & Nakao, K. (2018) · Journal of Gastroenterology · doi:10.1007/s00535-018-1451-5 · Cited by 79 · see citing works
Ghrelin Attenuated Lipotoxicity via Autophagy Induction and Nuclear Factor-κB Inhibition
Mao, Y., Cheng, J., Yu, F., Li, H., Guo, C., & Fan, X. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430377 · Cited by 75 · see citing works
Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy
Natarajan, S. K., & Ibdah, J. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010322 · Cited by 63 · see citing works
Self-citationBiliary NIK promotes ductular reaction and liver injury and fibrosis in mice
Zhang, Z., Zhong, X. Y., Shen, H., Sheng, L., Liangpunsakul, S., Lok, A. S.-F., Omary, M. B., Wang, S., & Rui, L. (2022) · Nature Communications · doi:10.1038/s41467-022-32575-8 · Cited by 56 · see citing works
Zika virus infection induces endoplasmic reticulum stress and apoptosis in placental trophoblasts
Muthuraj, P. G., Sahoo, P. K., Kraus, M., Bruett, T., Annamalai, A. S., Pattnaik, A., Pattnaik, A. K., Byrareddy, S. N., & Natarajan, S. K. (2021) · Cell Death Discovery · doi:10.1038/s41420-020-00379-8 · Cited by 54 · see citing works
Self-citationThe hedgehog pathway in nonalcoholic fatty liver disease
Machado, M. V., & Diehl, A. M. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1448752 · Cited by 52 · see citing works
Fred, R. G., Steen Pedersen, J., Thompson, J. J., Lee, J., Timshel, P. N., Stender, S., Opseth Rygg, M., Gluud, L. L., Bjerregaard Kristiansen, V., Bendtsen, F., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-16754-7 · Cited by 44 · see citing works
FoxO3 increases miR-34a to cause palmitate-induced cholangiocyte lipoapoptosis
Natarajan, S. K., Stringham, B. A., Mohr, A. M., Wehrkamp, C. J., Lu, S., Phillippi, M. A., Harrison-Findik, D. D., & Mott, J. L. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m071357 · Cited by 44 · see citing works
Self-citationNonalcoholic Steatohepatitis Drug Development Pipeline: An Update
Chew, N., Ng, C. H., Truong, E., Noureddin, M., & Kowdley, K. V. (2022) · Seminars in Liver Disease · doi:10.1055/a-1877-9656 · Cited by 43 · see citing works
Mitochondrial Dysfunction and Acute Fatty Liver of Pregnancy
Ramanathan, R., & Ibdah, J. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073595 · Cited by 42 · see citing works
Treating hyperuricemia related non-alcoholic fatty liver disease in rats with resveratrol
Xu, K., Liu, S., Zhao, X. D., Zhang, X., Fu, X., Zhou, Y., Xu, K., Miao, L., Li, Z., Li, Y., et al. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.12.039 · Cited by 38 · see citing works
Biliary Epithelial Senescence in Liver Disease: There Will Be SASP
Meadows, V., Baiocchi, L., Kundu, D., Sato, K., Fuentes, Y., Wu, C., Chakraborty, S., Glaser, S. S., Alpini, G. D., Kennedy, L. L., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.803098 · Cited by 36 · see citing works
Wu, Q., Zhao, M. F., He, X., Xue, R., Li, D., Yu, X., Wang, S., & Zang, W. (2021) · Cell Cycle · doi:10.1080/15384101.2021.1965734 · Cited by 34 · see citing works
Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes
Chen, L., Wu, N., Kennedy, L. L., Francis, H., Ceci, L., Zhou, T., Samala, N. R., Kyritsi, K., Wu, C., Sybenga, A. B., et al. (2021) · Hepatology · doi:10.1002/hep.31871 · Cited by 33 · see citing works
Wang, L., Zhu, X., Sun, X., Yang, X., Chang, X., Xia, M., Lu, Y., Xia, P., Yan, H., Bian, H., et al. (2019) · Lipids in Health and Disease · doi:10.1186/s12944-019-1132-2 · Cited by 32 · see citing works
Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease
Wu, C., Zhou, Y., Wang, M., Dai, G., Liu, X., Lai, L., & Tang, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.772487 · Cited by 30 · see citing works
Kyritsi, K., Francis, H., Zhou, T., Ceci, L., Wu, N., Yang, Z., Meng, F., Chen, L., Baiocchi, L., Kundu, D., et al. (2020) · Gene Expression · doi:10.3727/105221620x15889714507961 · Cited by 28 · see citing works
Saturated free fatty acids induce placental trophoblast lipoapoptosis
Natarajan, S. K., Bruett, T., Muthuraj, P. G., Sahoo, P. K., Power, J., Mott, J. L., Hanson, C., & Anderson‐Berry, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0249907 · Cited by 26 · see citing works
Self-citationZhou, T., Kundu, D., Robles-Linares, J., Meadows, V., Sato, K., Baiocchi, L., Ekser, B., Glaser, S. S., Alpini, G. D., Francis, H., et al. (2021) · Cells · doi:10.3390/cells10082072 · Cited by 25 · see citing works
Impact of Dietary Fat on the Progression of Liver Fibrosis: Lessons from Animal and Cell Studies
Jia, F., Hu, X., Kimura, T., & Tanaka, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910303 · Cited by 24 · see citing works
Dhingra, S., Mahadik, J. D., Tarabishy, Y., May, S., & Vierling, J. M. (2022) · Pathology · doi:10.1016/j.pathol.2022.01.009 · Cited by 23 · see citing works
Bile acid signaling in MASLD: From pathogenesis to therapeutic applications
Simbrunner, B., Paternostro, R., Reiberger, T., & Trauner, M. (2025) · Hepatology · doi:10.1097/hep.0000000000001539 · Cited by 26 · see citing works
Cellular heterogeneity and plasticity during NAFLD progression
Park, H., Choi, J., Kim, H.-M., Yang, D.-Y., An, T. H., Lee, E., Han, B., Lee, S. C., Kim, W. K., Bae, K., et al. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1221669 · Cited by 22 · see citing works
Han, D., Xu, K., Jin, Z., Xu, Y., Li, Y., Wang, L., Cao, Q., Kim, K.-P., Ryu, D. H., Hong, K., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.85145 · Cited by 21 · see citing works
Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH)
Wang, Z., Zhao, Z., Xia, Y., Cai, Z., Wang, C., Shen, Y., Liu, R., Qin, H., Jia, J., & Yuan, G. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01773-y · Cited by 17 · see citing works
Dou, X., Ding, Q., Lai, S., Jiang, F., Song, Q., Zhao, X., Fu, A., Moustaïd‐Moussa, N., Su, D., & Li, S. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103691 · Cited by 16 · see citing works
Zavorka, M. E., Connelly, C. M., Grosely, R., & MacDonald, R. G. (2016) · Oncotarget · doi:10.18632/oncotarget.11493 · Cited by 14 · see citing works
The Neglected Role of Bile Duct Epithelial Cells in NASH
Cadamuro, M., Lasagni, A., Sarcognato, S., Guido, M., Fabris, R., Strazzabosco, M., Strain, A. J., Simioni, P., Villa, E., & Fabris, L. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1739455 · Cited by 13 · see citing works
ARMCX3 Mediates Susceptibility to Hepatic Tumorigenesis Promoted by Dietary Lipotoxicity
Mirra, S., Gavaldà-Navarro, A., Manso, Y., Higuera, M., Serrat, R., Salcedo, M., Burgaya, F., Balibrea, J., Santamaría, E., Uriarte, I., et al. (2021) · Cancers · doi:10.3390/cancers13051110 · Cited by 11 · see citing works
High-fat diet promotes prostate cancer metastasis via RPS27
Li, D., Zhou, X., Wen-xian, X., Cai, Y., Mu, C., Zhao, X., Tang, T., Chen, L., Yang, T., Zheng, J., et al. (2024) · Cancer & Metabolism · doi:10.1186/s40170-024-00333-7 · Cited by 12 · see citing works
Palmitate induces integrated stress response and lipoapoptosis in trophoblasts
Sahoo, P. K., Krishnamoorthy, C., Wood, J. R., Hanson, C., Anderson‐Berry, A., Mott, J. L., & Natarajan, S. K. (2024) · Cell Death and Disease · doi:10.1038/s41419-023-06415-6 · Cited by 12 · see citing works
Self-citationHuang, Y., Jiang, J., Wang, W., Guo, J., Yang, N., Zhang, J., Liu, Q., Chen, Y., Hu, T., & Rao, C. (2022) · Toxicon · doi:10.1016/j.toxicon.2022.08.008 · Cited by 12 · see citing works
Wan, Z., Liu, X., Yang, X., Huang, Z., Chen, X., Feng, Q., Cao, H., & Hong, D. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05434-6 · Cited by 11 · see citing works
FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases
Chang, Z., He, Z., & Xia, J. (2022) · Current Molecular Medicine · doi:10.2174/1566524023666221014140817 · Cited by 9 · see citing works
Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
Muthuraj, P. G., Pattnaik, A., Sahoo, P. K., Islam, M. T., Pattnaik, A. K., Byrareddy, S. N., Hanson, C., Anderson‐Berry, A., Kachman, S. D., & Natarajan, S. K. (2021) · Biomedicines · doi:10.3390/biomedicines9060643 · Cited by 9 · see citing works
Self-citationMouse serum albumin induces neuronal apoptosis and tauopathies
Hou, S., Huang, Y., Zhu, J., Jia, Y., Niu, X.-Y., Yang, J.-J., Yu, X., Du, X.-Y., Liang, S., Cui, F., et al. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01771-6 · Cited by 8 · see citing works
Palmitoleate protects against lipopolysaccharide-induced inflammation and inflammasome activity
Sahoo, P. K., Ravi, A., Liu, B., Yu, J., & Natarajan, S. K. (2024) · Journal of Lipid Research · doi:10.1016/j.jlr.2024.100672 · Cited by 8 · see citing works
Self-citationCholangiocyte lipoapoptosis: Implications for biliary damage during nonalcoholic fatty liver disease
Martínez, A. K., & Glaser, S. S. (2014) · Hepatology · doi:10.1002/hep.27341 · Cited by 7 · see citing works
Lin, J., Wu, T., Wang, C., Zhou, W., Liu, Y., Yang, G., Zhou, H., Luo, J., Fan, Z., Da, Y., et al. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156623 · Cited by 2 · see citing works
Hu, J., & Chen, X. (2019) · Non-coding RNA Investigation · doi:10.21037/ncri.2019.02.03 · Cited by 2 · see citing works
El-Shafie, M., Allam, H., Shall, L. Y. E., Abdel‐Samiee, M., Ibrahim, E. H., Khalaf, F. M., & Ali, S. (2017) · World Journal of Research and Review · Cited by 2 · see citing works
The Role of Cholangiocyte Cell Death in the Development of Biliary Diseases
O’Brien, A., Hall, C. M., Ehrlich, L., Zhou, T., Meng, F., Alpini, G. D., & Glaser, S. S. (2017) · Springer eBooks · doi:10.1007/978-3-319-58106-4_2 · Cited by 1 · see citing works
Necrobiology of Liver Cancer: Other Forms of Cell Death Related or not Related to Apoptosis
Zimmermann, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-26587-2_177-1
Lipotoxicity in Non-parenchymal Liver Cells
Harris, E. N., & Mott, J. L. (2017) · Springer eBooks · doi:10.1007/978-3-319-58106-4_1
Self-citation3-Hydroxy Fatty Acids Induce Retinal Pigment Epithelial Cell Lipoapoptosis
Hadidi, M. (2019) · Lincoln (University of Nebraska)
Liver Cirrhosis with Steatohepatitis: Nonalcoholic Steatohepatitis and Alcoholic Steatohepatitis
Miyake, T., & Hiasa, Y. (2019) · Springer eBooks · doi:10.1007/978-981-13-7979-6_1
Necrobiology of Liver Cancer: Other Forms of Cell Death Related or Not Related to Apoptosis
Zimmermann, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-26956-6_177
Additional file 1 of Mouse serum albumin induces neuronal apoptosis and tauopathies
Hou, S.-J., Huang, Y.-R., Zhu, J., Jia, Y.-B., Niu, X.-Y., Yang, J.-J., Yu, X.-L., Du, X.-Y., Liang, S.-Y., Cui, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26710775
Additional file 1 of High-fat diet promotes prostate cancer metastasis via RPS27
Li, D., Zhou, X., Xu, W., Cai, Y., Mu, C., Zhao, X., Tang, T., Liang, C., Yang, T., Zheng, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25237388
Additional file 2 of Mouse serum albumin induces neuronal apoptosis and tauopathies
Hou, S.-J., Huang, Y.-R., Zhu, J., Jia, Y.-B., Niu, X.-Y., Yang, J.-J., Yu, X.-L., Du, X.-Y., Liang, S.-Y., Cui, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26710778
Additional file 3 of Mouse serum albumin induces neuronal apoptosis and tauopathies
Hou, S.-J., Huang, Y.-R., Zhu, J., Jia, Y.-B., Niu, X.-Y., Yang, J.-J., Yu, X.-L., Du, X.-Y., Liang, S.-Y., Cui, F., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26710781
N-methyl-D-aspartate receptor inhibition protects against obesity-induced kidney disease
Eritja, À., Pérez-Olives, C., Falcón, D. A. R., Caus, M., García-Carrasco, A., Bardaji, A. M., Escalante, E. J., Martin, M., van Zonneveld, A. J., Bijkerk, R., et al. (2026) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfag027
Role of autophagy in liver sinusoidal endothelial cells on nonalcoholic steatohepatitis
Hammoutène, A. (2018) · theses.fr (ABES) · doi:10.70675/bce7a140z3574z43dbza40ez1cd3403ed525
刘连勇, Hu, G., Gu, F., Zhu, Q., Li, C., Di, X., Zou, M., & Li, X. (2026) · Internal and Emergency Medicine · doi:10.1007/s11739-026-04553-1
- Authors
- Natarajan, S. K., Ingham, S. A., Mohr, A. M., Wehrkamp, C. J., Ray, A., Roy, S., Cazanave, S. C., Phillippi, M. A., & Mott, J. L.
- Affiliations
- Nebraska Medical Center (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Mott, Justin L.
- ORCID
- Venue
- Hepatology
- Published
- 2014-06-20
- Volume
- 60
- Issue
- 6
- Pages
- 1942-1956
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC4553418
- OpenAlex
- W2115873611
- Cited by
- 62
- References
- 53
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 10 · 2023: 3 · 2022: 8 · 2021: 13 · 2020: 1 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 1
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- DigitalCommons@UNMC (submittedVersion)
- Funders
- Fred & Pamela Buffett Cancer Center
- University of Nebraska Medical Center
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- lipoapoptosis, cholangiocytes, saturated free fatty acids, palmitate, stearate, nonalcoholic steatohepatitis, caspase-3/7 activation, PUMA, FOXO3, post-translational modification, nuclear translocation, cholangiocyte injury
- MeSH terms
- Forkhead Box Protein O3, Bile Ducts, Intrahepatic, Enzyme Activation, Fatty Acids, Nonesterified, Fatty Liver, Humans, Palmitates, Proto-Oncogene Proteins, Apoptosis, Caspases, Mitogen-Activated Protein Kinases, Cell Line, Tumor, Apoptosis Regulatory Proteins, Forkhead Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
