Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling

Schattenberg, Jörn M.; Wang, Yongjun; Singh, Rajat; Rigoli, Raina M.; Czaja, Mark J.

doi:10.1074/jbc.m410310200

Cited by 194Liver Disease Diagnosis and TreatmentLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling

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Schattenberg, Jörn M., Wang, Yongjun, Singh, Rajat, Rigoli, Raina M., Czaja, Mark J.·2005·Journal of Biological Chemistry

DOI 10.1074/jbc.m410310200

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Abstract

Insulin resistance and increased cytochrome P450 2E1 (CYP2E1) expression are both associated with and mechanistically implicated in the development of nonalcoholic fatty liver disease. Although currently viewed as distinct factors, insulin resistance and CYP2E1 expression may be interrelated through the ability of CYP2E1-induced oxidant stress to impair hepatic insulin signaling. To test this possibility, the effects of in vitro and in vivo CYP2E1 overexpression on hepatocyte insulin signaling were examined. CYP2E1 overexpression in a hepatocyte cell line decreased tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 in response to insulin. CYP2E1 overexpression was also associated with increased inhibitory serine 307 and 636/639 IRS-1 phosphorylation. In parallel, the effects of insulin on Akt activation, glycogen synthase kinase 3, and FoxO1a phosphorylation, and glucose secretion were all significantly decreased in CYP2E1 overexpressing cells. This inhibition of insulin signaling by CYP2E1 overexpression was partially c-Jun N-terminal kinase dependent. In the methionine- and choline-deficient diet mouse model of steatohepatitis with CYP2E1 overexpression, insulin-induced IRS-1, IRS-2, and Akt phosphorylation were similarly decreased. These findings indicate that increased hepatocyte CYP2E1 expression and the presence of steatohepatitis result in the down-regulation of insulin signaling, potentially contributing to the insulin resistance associated with nonalcoholic fatty liver disease.

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Activation of JNK is positively related to high fat diet-induced insulin resistance and metabolic syndrome.
“In addition, activation of JNK was positively related to high fat diet-induced insulin resistance and metabolic syndrome [119], [121], [122], [123].”
From Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications (2014) · cites this paper as [121]

Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326 · see citing works
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244 · see citing works
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome
Marchesini, G., Bugianesi, E., Forlani, G., Cerrelli, F., Lenzi, M., Manini, R., Natale, S., Vanni, E., Villanova, N., Melchionda, N., et al. (2003) · Hepatology · doi:10.1053/jhep.2003.50161 · Cited by 2,676 · see citing works
Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002) · Endocrine Reviews · doi:10.1210/er.2001-0039 · Cited by 2,232 · see citing works
Nonalcoholic Steatohepatitis: Summary of An Aasld Single Topic Conference
Neuschwander‐Tetri, B. A., & Caldwell, S. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50193 · Cited by 2,155 · see citing works
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078 · see citing works
Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,837 · see citing works
Number and evolutionary conservation of α- and β-tubulin and cytoplasmic β- and γ-actin genes using specific cloned cDNA probes
Cleveland, D. W., Lopata, M. A., MacDonald, R. J., Cowan, N. J., Rutter, W. J., & Kirschner, M. W. (1980) · Cell · doi:10.1016/0092-8674(80)90238-x · Cited by 1,835 · see citing works
Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction
Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487 · see citing works
The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307
Aguirre, V., Uchida, T., Yenush, L., Davis, R., & White, M. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.9047 · Cited by 1,487 · see citing works
Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322 · see citing works
NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome
Chitturi, S., Abeygunasekera, S., Farrell, G. C., Holmes-Walker, J., Hui, J. M., Fung, C., Karim, R., Lin, R., Samarasinghe, D., Liddle, C., et al. (2002) · Hepatology · doi:10.1053/jhep.2002.30692 · Cited by 1,122 · see citing works
Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1
Tamemoto, H., Kadowaki, T., Tobe, K., Yagi, T., Sakura, H., Hayakawa, T., Terauchi, Y., Ueki, K., Kaburagi, Y., Satoh, S., et al. (1994) · Nature · doi:10.1038/372182a0 · Cited by 1,082 · see citing works
PKB/Akt
Lawlor, M. A., & Alessi, D. R. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.16.2903 · Cited by 1,071 · see citing works
Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Virkamäki, A., Ueki, K., & Kahn, C. R. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6609 · Cited by 854 · see citing works
Serine Phosphorylation of Insulin Receptor Substrate 1 by Inhibitor κB Kinase Complex
Gao, Z., Hwang, D. H., Bataille, F., Lefevre, M., York, D. A., Quon, M. J., & Ye, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209459200 · Cited by 777 · see citing works
CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis
Leclercq, I. A., Farrell, G. C., Field, J., Bell, D., Gonzalez, F. J., & Robertson, G. R. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8814 · Cited by 763 · see citing works
Negative Regulation of the Forkhead Transcription Factor FKHR by Akt
Tang, E., Núñez, G., Barr, F. G., & Guan, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.16741 · Cited by 761 · see citing works
Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association
Pagano, G., Pacini, G., Musso, G., Gambino, R., Mecca, F., Depetris, N., Cassader, M., David, E., Cavallo‐Perin, P., & Rizzetto, M. (2002) · Hepatology · doi:10.1053/jhep.2002.30690 · Cited by 754 · see citing works
Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ
Garofalo, R. S., Orena, S. J., Rafidi, K., Torchia, A. J., Stock, J. L., Hildebrandt, A. L., Coskran, T., Black, S. C., Brees, D. J., Wicks, J. R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16885 · Cited by 726 · see citing works
The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression
Nakae, J., Kitamura, T., Silver, D. L., & Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12876 · Cited by 652 · see citing works
The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression
Nakae, J., Kitamura, T., Silver, D. L., & Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112876 · Cited by 652 · see citing works
Suppressor of Cytokine Signaling-3 (SOCS-3), a Potential Mediator of Interleukin-6-dependent Insulin Resistance in Hepatocytes
Senn, J. J., Klover, P. J., Nowak, I. A., Zimmers, T. A., Koniaris, L. G., Furlanetto, R. W., & Mooney, R. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210689200 · Cited by 620 · see citing works
Regulation of insulin action and pancreatic β-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1
Nakae, J., Biggs, W., Kitamura, T., Cavenee, W. K., Wright, C. V. E., Arden, K. C., & Accili, D. (2002) · Nature Genetics · doi:10.1038/ng890 · Cited by 616 · see citing works
Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis
Weltman, M., Farrell, G. C., Hall, P. D. L. Μ., Ingelman‐Sundberg, M., & Liddle, C. (1998) · Hepatology · doi:10.1002/hep.510270121 · Cited by 613 · see citing works
Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1)
Ekström, G., & Ingelman‐Sundberg, M. (1989) · Biochemical Pharmacology · doi:10.1016/0006-2952(89)90338-9 · Cited by 528 · see citing works
Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2
Kido, Y., Burks, D. J., Withers, D. J., Brüning, J. C., Kahn, C. R., White, M. F., & Accili, D. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7917 · Cited by 491 · see citing works
The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance
Rinella, M. E., & Green, R. M. (2003) · Journal of Hepatology · doi:10.1016/j.jhep.2003.09.020 · Cited by 462 · see citing works
NFkappaB prevents apoptosis and liver dysfunction during liver regeneration.
Iimuro, Y., Nishiura, T., Hellerbrand, C., Behrns, K. E., Schoonhoven, R., Grisham, J. W., & Brenner, D. A. (1998) · Journal of Clinical Investigation · doi:10.1172/jci483 · Cited by 447 · see citing works
c-Jun N-terminal Kinase (JNK) Mediates Feedback Inhibition of the Insulin Signaling Cascade
Lee, Y. H., Giraud, J., Davis, R. J., & White, M. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208359200 · Cited by 441 · see citing works
Nopp 140 shuttles on tracks between nucleolus and cytoplasm
Meier, U. T., & Blobel, G. (1992) · Cell · doi:10.1016/0092-8674(92)90539-o · Cited by 424 · see citing works
Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide
Kaneto, H., Nakatani, Y., Miyatsuka, T., Kawamori, D., Matsuoka, T., Matsuhisa, M., Kajimoto, Y., Ichijo, H., Yamasaki, Y., & Hori, M. (2004) · Nature Medicine · doi:10.1038/nm1111 · Cited by 337 · see citing works
Phosphorylation of Serine 256 Suppresses Transactivation by FKHR (FOXO1) by Multiple Mechanisms
Zhang, X., Gan, L., Pan, H., Guo, S., He, X., Olson, S. T., Mesecar, A. D., Adam, S. A., & Unterman, T. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208063200 · Cited by 294 · see citing works
Regulation of Phosphoenolpyruvate Carboxykinase and Insulin-like Growth Factor-binding Protein-1 Gene Expression by Insulin
Hall, R. K., Yamasaki, T., Kučera, T., Waltner-Law, M. E., O’Brien, R. M., & Granner, D. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004898200 · Cited by 283 · see citing works
Modulation of the JNK Pathway in Liver Affects Insulin Resistance Status
Nakatani, Y., Kaneto, H., Kawamori, D., Hatazaki, M., Miyatsuka, T., Matsuoka, T., Kajimoto, Y., Matsuhisa, M., Yamasaki, Y., & Hori, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406963200 · Cited by 230 · see citing works
Rat hepatic cytosolic phosphoenolpyruvate carboxykinase (GTP). Structures of the protein, messenger RNA, and gene.
BEALE, E. G., Chrapkiewicz, N. B., Scoble, H. A., Metz, R. J., Quick, D. P., Noble, R., Donelson, J. E., BIEMANN, K., & Granner, D. K. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85145-1 · Cited by 221 · see citing works
NF-κB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun
Liu, H., Lo, C. R., & Czaja, M. J. (2002) · Hepatology · doi:10.1053/jhep.2002.32534 · Cited by 199 · see citing works
Diabetes mellitus increases the in vivo activity of cytochrome P450 2E1 in humans
Wang, Z., Hall, S. D., Maya, J. F., Li, L., Asghar, A., & Gorski, J. C. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01731.x · Cited by 197 · see citing works
c‐Jun N‐terminal kinases (JNK) antagonize cardiac growth through cross‐talk with calcineurin–NFAT signaling
Liang, Q., Bueno, O. F., Wilkins, B. J., Kuan, C.-Y., Xia, Y., & Molkentin, J. D. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg474 · Cited by 197 · see citing works
PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity
Matsumoto, M., Ogawa, W., Akimoto, K., Inoue, H., Miyake, K., Furukawa, K., Hayashi, Y., Iguchi, H., Matsuki, Y., Hiramatsu, R., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18816 · Cited by 176 · see citing works
Hepatic Akt Activation Induces Marked Hypoglycemia, Hepatomegaly, and Hypertriglyceridemia With Sterol Regulatory Element Binding Protein Involvement
Ono, H., Shimano, H., Katagiri, H., Yahagi, N., Sakoda, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Viana, A. Y. I., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.12.2905 · Cited by 170 · see citing works
PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity
Matsumoto, M., Ogawa, W., Akimoto, K., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318816 · Cited by 152 · see citing works
Secretion, Surface Localization, Turnover, and Steady State Expression of Protein Disulfide Isomerase in Rat Hepatocytes
Terada, K., Manchikalapudi, P., Noiva, R., Jauregui, H. O., Stockert, R. J., & Schilsky, M. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.35.20410 · Cited by 149 · see citing works
Molecular Mechanisms of Insulin Resistance in IRS-2-Deficient Hepatocytes
Valverde, Á. M., Burks, D. J., Fabregat, I., Fisher, T. L., Carretero, J., White, M. F., & Benito, M. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2239 · Cited by 144 · see citing works
p53 Involvement in the Pathogenesis of Fatty Liver Disease
Yahagi, N., Shimano, H., Matsuzaka, T., Sekiya, M., Najima, Y., Okazaki, S., Okazaki, H., Tamura, Y., Iizuka, Y., Inoue, N., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400884200 · Cited by 126 · see citing works
Nutrient-dependent and Insulin-stimulated Phosphorylation of Insulin Receptor Substrate-1 on Serine 302 Correlates with Increased Insulin Signaling
Giraud, J., Leshan, R. L., Lee, Y.-H., & White, M. F. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308631200 · Cited by 100 · see citing works
Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by protein kinase Cdelta
Greene, M. W., MORRICE, N. A., Garofalo, R. S., & Roth, R. A. (2004) · Biochemical Journal · doi:10.1042/bj20031493 · Cited by 89 · see citing works
Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway
Hirashima, Y., Tsuruzoe, K., Kodama, S., Igata, M., Toyonaga, T., Ueki, K., Kahn, C. R., & Araki, E. (2003) · Journal of Endocrinology · doi:10.1677/joe.0.1790253 · Cited by 89 · see citing works
Virtual cloning, functional expression, and gating analysis of human connexin31.9
White, T. W., Srinivas, M., Ripps, H., Salinaro, A. T., Condorelli, D. F., & Bruzzone, R. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00163.2002 · Cited by 84 · see citing works
Hyperosmotic Stress Inhibits Insulin Receptor Substrate-1 Function by Distinct Mechanisms in 3T3-L1 Adipocytes
Gual, P., Gonzalez, T., Grémeaux, T., Barrès, R., MARCHAND‐BRUSTEL, Y. L., & Tanti, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212273200 · Cited by 79 · see citing works
CYP2E1 overexpression alters hepatocyte death from menadione and fatty acids by activation of ERK1/2 signaling
Schattenberg, J. M., Wang, Y., Rigoli, R. M., Koop, D. R., & Czaja, M. J. (2004) · Hepatology · doi:10.1002/hep.20067 · Cited by 66 · see citing works
Glutamate Regulates Kainate-binding Protein Expression in Cultured Chick Bergmann Glia through an Activator Protein-1 Binding Site
Aguirre, A. A., López, T., López‐Bayghen, E., & Ortega, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002847200 · Cited by 61 · see citing works
Temperature-sensitive adult liver cell line dependent on glucocorticoid for differentiation.
CHOU, J. Y. (1983) · Molecular and Cellular Biology · doi:10.1128/mcb.3.6.1013 · Cited by 55 · see citing works
Fatty liver, hypertension, and the metabolic syndrome
Diehl, A. M. (2004) · Gut · doi:10.1136/gut.2003.037309 · Cited by 51 · see citing works
Oxidative stress impairs insulin but not platelet-derived growth factor signalling in 3T3-L1 adipocytes
Tirosh, A., Rudich, A., Potashnik, R., & Bashan, N. (2001) · Biochemical Journal · doi:10.1042/bj3550757 · Cited by 42 · see citing works
Inhibition of c-Myc Expression Sensitizes Hepatocytes to Tumor Necrosis Factor-induced Apoptosis and Necrosis
Liu, H., Lo, C. R., Jones, B., Pradhan, Z., Srinivasan, A. N., Valentino, K. L., Stockert, R. J., & Czaja, M. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001565200 · Cited by 38 · see citing works
Cytochrome P450 2E1 Expression Induces Hepatocyte Resistance to Cell Death from Oxidative Stress
Jones, B., Liu, H., Lo, C. R., Koop, D. R., & Czaja, M. J. (2002) · Antioxidants and Redox Signaling · doi:10.1089/152308602760598846 · Cited by 35 · see citing works
Amplification of the metallothionein‐1 and metallothionein‐2 genes in copper‐resistant hepatoma cells
Czaja, M. J., Weiner, F. R., & Freedman, J. H. (1991) · Journal of Cellular Physiology · doi:10.1002/jcp.1041470308 · Cited by 22 · see citing works
Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase α
Le, H., Ponniah, S., & Pallen, C. J. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.12.087 · Cited by 13 · see citing works

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Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975 · see citing works
Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis
Farrell, G. C., & Larter, C. Z. (2006) · Hepatology · doi:10.1002/hep.20973 · Cited by 2,413 · see citing works
Inflammatory mechanisms in the regulation of insulin resistance
Tilg, H., & Moschen, A. R. (2008) · Molecular Medicine · doi:10.2119/2007-00119.tilg · Cited by 779 · see citing works
Mitochondrial dysfunction in Nash: causes, consequences and possible means to prevent it
Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B. (2006) · Mitochondrion · doi:10.1016/j.mito.2005.10.004 · Cited by 753 · see citing works
Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research
Anstee, Q. M., & Goldin, R. D. (2006) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2006.00465.x · Cited by 714 · see citing works
Apoptosis and Necrosis in the Liver: A Tale of Two Deaths?
Malhi, H., Gores, G. J., & Lemasters, J. J. (2006) · Hepatology · doi:10.1002/hep.21062 · Cited by 688 · see citing works
An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis
Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M. (2013) · International Journal of Experimental Pathology · doi:10.1111/iep.12008 · Cited by 523 · see citing works
Non alcoholic fatty liver disease and metabolic syndrome.
Paschos, P., & Paletas, K. (2009) · PubMed Central · Cited by 539 · see citing works
Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease
Paradies, G. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i39.14205 · Cited by 508 · see citing works
Animal models of nonalcoholic fatty liver disease
Hebbard, L., & George, J. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.191 · Cited by 495 · see citing works
Mechanisms of Disease Progression in Nonalcoholic Fatty Liver Disease
Jou, J. H., Choi, S. S., & Diehl, A. M. (2008) · Seminars in Liver Disease · doi:10.1055/s-0028-1091981 · Cited by 482 · see citing works
Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet
Rinella, M. E., Elias, M. S., Smolak, R. R., Fu, T., Borensztajn, J., & Green, R. M. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800042-jlr200 · Cited by 451 · see citing works
Redox mechanisms in hepatic chronic wound healing and fibrogenesis
Novo, E., & Parola, M. (2008) · Fibrogenesis & Tissue Repair · doi:10.1186/1755-1536-1-5 · Cited by 406 · see citing works
JNK1 but not JNK2 promotes the development of steatohepatitis in mice
Schattenberg, J. M., Singh, R., Wang, Y., Lefkowitch, J. H., Rigoli, R. M., Scherer, P. E., & Czaja, M. J. (2006) · Hepatology · doi:10.1002/hep.20999 · Cited by 384 · see citing works
Nonalcoholic Fatty Liver Disease: Cytokine-Adipokine Interplay and Regulation of Insulin Resistance
Tilg, H., & Hotamışlıgil, G. S. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.05.054 · Cited by 385 · see citing works
Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease
Machado, M. V., Michelotti, G. A., Xie, G., Pereira, T. A., Boursier, J., Bohnic, B., Guy, C. D., & Diehl, A. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127991 · Cited by 381 · see citing works
Insulin resistance in hepatocytes and sinusoidal liver cells: Mechanisms and consequences
Leclercq, I. A., Morais, A. D. S., Schroyen, B., Hul, N. V., & Geerts, A. E. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.04.002 · Cited by 359 · see citing works
Apoptosis and Necrosis in the Liver
Guicciardi, M. E., Malhi, H., Mott, J. L., & Gores, G. J. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120020 · Cited by 387 · see citing works
Animal models of NASH: Getting both pathology and metabolic context right
Larter, C. Z., & Yeh, M. M. (2008) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2008.05543.x · Cited by 337 · see citing works
Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment
Smith, B. W., & Adams, L. A. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.72 · Cited by 327 · see citing works
Recent concepts in non‐alcoholic fatty liver disease
Adams, L. A., & Angulo, P. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01748.x · Cited by 324 · see citing works
Mouse Models of Nonalcoholic Steatohepatitis: Toward Optimization of Their Relevance to Human Nonalcoholic Steatohepatitis
Farrell, G., Schattenberg, J. M., Leclercq, I., Yeh, M. M., Goldin, R., Teoh, N., & Schuppan, D. (2019) · Hepatology · doi:10.1002/hep.30333 · Cited by 313 · see citing works
Molecular Mechanisms of Alcoholic Fatty Liver
Purohit, V., Gao, B., & Song, B. (2009) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00827.x · Cited by 312 · see citing works
Oxidative mechanisms in the pathogenesis of alcoholic liver disease
Albano, E. (2007) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2007.09.004 · Cited by 303 · see citing works
Histological assessment of non‐alcoholic fatty liver disease
Hübscher, S. G. (2006) · Histopathology · doi:10.1111/j.1365-2559.2006.02416.x · Cited by 292 · see citing works
Non-alcoholic fatty liver disease
Smith, B. W., & Adams, L. A. (2011) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2011.596521 · Cited by 288 · see citing works
Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease
Tamura, S., & Shimomura, I. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24930 · Cited by 288 · see citing works
Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: Mechanisms and pathophysiological role
Aubert, J., Begriche, K., Knockaert, L., Robin, M., & Fromenty, B. (2011) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2011.04.015 · Cited by 282 · see citing works
Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease
Qureshi, K. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i26.3540 · Cited by 282 · see citing works
Molecular mechanisms involved in NAFLD progression
Malaguarnera, M., Rosa, M. D., Nicoletti, F., & Malaguarnera, L. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0464-1 · Cited by 281 · see citing works
Hepatic Microcirculation in Fatty Liver Disease
Farrell, G. C., Teoh, N., & McCuskey, R. S. (2008) · The Anatomical Record · doi:10.1002/ar.20715 · Cited by 268 · see citing works
A Model of Insulin Resistance and Nonalcoholic Steatohepatitis in Rats
Svegliati‐Baroni, G., Candelaresi, C., Saccomanno, S., Ferretti, G., Bachetti, T., Marzioni, M., Minicis, S. D., Nobili, L., Salzano, R., Omenetti, A., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050953 · Cited by 256 · see citing works
Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis
Abdelmegeed, M. A., Banerjee, A., Yoo, S.-H., Jang, S., Gonzalez, F. J., & Song, B. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.019 · Cited by 241 · see citing works
Insulin Resistance Accelerates a Dietary Rat Model of Nonalcoholic Steatohepatitis
Ota, T., Takamura, T., Kurita, S., Matsuzawa, N., Kita, Y., Uno, M., Akahori, H., Misu, H., Sakurai, M., Zen, Y., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.10.014 · Cited by 227 · see citing works
Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance†
Singh, R., Wang, Y., Xiang, Y., Tanaka, K. E., Gaarde, W. A., & Czaja, M. J. (2008) · Hepatology · doi:10.1002/hep.22578 · Cited by 224 · see citing works
Impaired de Novo Choline Synthesis Explains Why Phosphatidylethanolamine N-Methyltransferase-deficient Mice Are Protected from Diet-induced Obesity
Jacobs, R. L., Zhao, Y., Koonen, D. P. Y., Sletten, T., Su, B., Lingrell, S., Cao, G., Peake, D. A., Kuo, M., Proctor, S. D., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.108514 · Cited by 212 · see citing works
A Choline-Deficient Diet Exacerbates Fatty Liver but Attenuates Insulin Resistance and Glucose Intolerance in Mice Fed a High-Fat Diet
Raubenheimer, P. J., Nyirenda, M., & Walker, B. R. (2006) · Diabetes · doi:10.2337/db06-0097 · Cited by 199 · see citing works
Current concepts in the pathogenesis of nonalcoholic fatty liver disease
Méndez‐Sánchez, N., Arrese, M. A., Zamora‐Valdés, D., & Uribe, M. (2007) · Liver International · doi:10.1111/j.1478-3231.2007.01483.x · Cited by 184 · see citing works
Non‐alcoholic fatty liver disease: Further expression of the metabolic syndrome
Tarantino, G., Saldalamacchia, G., Conca, P., & Arena, A. (2007) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2007.04824.x · Cited by 184 · see citing works
Pediatric nonalcoholic fatty liver disease (NAFLD): A “growing” problem?
Roberts, E. A. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.03.003 · Cited by 180 · see citing works
A fresh look at NASH pathogenesis. Part 1: The metabolic movers
Larter, C. Z., Chitturi, S., Heydet, D., & Farrell, G. C. (2010) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2010.06253.x · Cited by 178 · see citing works
Nonalcoholic Fatty Liver Disease as a Complication of Insulin Resistance
Abdelmalek, M. F., & Diehl, A. M. (2007) · Medical Clinics of North America · doi:10.1016/j.mcna.2007.06.001 · Cited by 169 · see citing works
Pathogenesis of alcohol‐induced liver disease: Classical concepts and recent advances
Seth, D., Haber, P. S., Syn, W., Diehl, A. M., & Day, C. P. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.06756.x · Cited by 166 · see citing works
Insulin resistance, adiponectin, cytokines in NASH: Which is the best target to treat?
Larter, C. Z., & Farrell, G. C. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.11.030 · Cited by 154 · see citing works
Apoptosis in liver disease
Schattenberg, J. M., Galle, P. R., & Schuchmann, M. (2006) · Liver International · doi:10.1111/j.1478-3231.2006.01324.x · Cited by 144 · see citing works
High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling
Xie, D., Zhao, H., Lu, J., He, F., Liu, W., Yu, W., Wang, Q., Hisatome, I., Yamamoto, T., Koyama, H., et al. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00518.2020 · Cited by 143 · see citing works
Animal Models of Non-Alcoholic Steatohepatitis: Of Mice and Man
Schattenberg, J. M., & Galle, P. R. (2010) · Digestive Diseases · doi:10.1159/000282097 · Cited by 140 · see citing works
MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes
Larter, C. Z., Yeh, M. M., Williams, J., Bell-Anderson, K. S., & Farrell, G. C. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.03.026 · Cited by 133 · see citing works
Loss of Macroautophagy Promotes or Prevents Fibroblast Apoptosis Depending on the Death Stimulus
Wang, Y., Singh, R., Massey, A. C., Kane, S. S., Kaushik, S., Grant, T., Xiang, Y., Cuervo, A. M., & Czaja, M. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706666200 · Cited by 132 · see citing works
Update on non-alcoholic fatty liver disease in children
Papandreou, D., Rousso, I., & Mavromichalis, I. (2007) · Clinical Nutrition · doi:10.1016/j.clnu.2007.02.002 · Cited by 126 · see citing works
Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity
INSERM, U., & Fromenty, B. (2017) · Journal of Clinical and Translational Research · doi:10.18053/jctres.03.2017s1.006 · Cited by 124 · see citing works
JNK regulation of hepatic manifestations of the metabolic syndrome
Czaja, M. J. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.08.010 · Cited by 124 · see citing works
Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123 · see citing works
“In addition, activation of JNK was positively related to high fat diet-induced insulin resistance and metabolic syndrome [119,121–123].”
Background
A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet
Baumgardner, J. N., Shankar, K., Hennings, L. J., Badger, T. M., & Ronis, M. J. J. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00296.2007 · Cited by 121 · see citing works
Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease
Panasiuk, A. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i38.6198 · Cited by 121 · see citing works
Drug-induced fatty liver disease: An overview of pathogenesis and management
Satapathy, S. K., Kuwajima, V. K., Nadelson, J., Atiq, O., & Sanyal, A. J. (2015) · Annals of Hepatology · doi:10.5604/16652681.1171749 · Cited by 120 · see citing works
Nonalcoholic steatohepatitis
Schattenberg, J. M., & Schuppan, D. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834c7cfc · Cited by 119 · see citing works
Synergistic association between alcohol intake and body mass index with serum alanine and aspartate aminotransferase levels in older adults: the Rancho Bernardo Study
Loomba, R. S., Bettencourt, R., & Barrett-Connor, E. L. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.04141.x · Cited by 110 · see citing works
Pathogenesis of NASH: Animal Models
London, R. M., & George, J. (2007) · Clinics in Liver Disease · doi:10.1016/j.cld.2007.02.010 · Cited by 108 · see citing works
Astaxanthin restricts weight gain, promotes insulin sensitivity and curtails fatty liver disease in mice fed a obesity-promoting diet
Bhuvaneswari, S., Elumalai, A., Viswanathan, P., & Anuradha, C. V. (2010) · Process Biochemistry · doi:10.1016/j.procbio.2010.05.016 · Cited by 107 · see citing works
Role of CYP2E1 in Mitochondrial Dysfunction and Hepatic Injury by Alcohol and Non-Alcoholic Substances
Abdelmegeed, M. A., Ha, S.-K., Choi, Y., Akbar, M. D., & Song, B. (2017) · Current Molecular Pharmacology · doi:10.2174/1874467208666150817111114 · Cited by 102 · see citing works
Melatonin application in targeting oxidative‐induced liver injuries: A review
Mortezaee, K., & Khanlarkhani, N. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26209 · Cited by 102 · see citing works
Cytochrome P- 450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance
Zong, H., Armoni, M., Harel, C., Karnieli, E., & Pessin, J. E. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00258.2011 · Cited by 101 · see citing works
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
Schattenberg, J. M., & Czaja, M. J. (2014) · Redox Biology · doi:10.1016/j.redox.2014.09.004 · Cited by 98 · see citing works
Pathogenesis of alcoholic liver disease
Sugimoto, K., & Takei, Y. (2016) · Hepatology Research · doi:10.1111/hepr.12736 · Cited by 98 · see citing works
Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease
Nobili, V., Manco, M., Ciampalini, P., Ciommo, V. M. D., Vito, R. D., Piemonte, F., Comparcola, D., Guidi, R., & Marcellini, M. (2006) · European Journal of Endocrinology · doi:10.1530/eje.1.02288 · Cited by 94 · see citing works
“Second Hit” Models of Alcoholic Liver Disease
Tsukamoto, H., Machida, K., Dynnyk, A., & Mkrtchyan, H. (2009) · Seminars in Liver Disease · doi:10.1055/s-0029-1214373 · Cited by 93 · see citing works
Intrahepatic insulin resistance in a murine model of steatohepatitis: effect of PPARγ agonist pioglitazone
Leclercq, I. A., Lebrun, V. A., Stärkel, P., & Horsmans, Y. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700489 · Cited by 90 · see citing works
Xanthine Oxidase Inhibition Attenuates Insulin Resistance and Diet-Induced Steatohepatitis in Mice
Nishikawa, T., Nagata, N., Shimakami, T., Shirakura, T., Matsui, C., Ni, Y., Zhuge, F., Xu, L., Chen, G., Nagashimada, M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-020-57784-3 · Cited by 84 · see citing works
Hepatic steatosis: A benign disease or a silent killer
El‐Zayadi, A. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4120 · Cited by 83 · see citing works
Carotenoids and non-alcoholic fatty liver disease.
Yılmaz, B., Şahin, K., Bilen, H., Bahçecioğlu, İ. H., Bilir, B., Ashraf, S., Halazun, K. J., & Küçük, Ö. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2304-3881.2015.01.11 · Cited by 83 · see citing works
Non-alcoholic fatty liver disease and insulin resistance
Machado, M. V., & Cortez‐Pinto, H. (2005) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200508000-00008 · Cited by 79 · see citing works
Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN
Piguet, A., Stroka, D., Zimmermann, A., & Dufour, J. (2009) · Clinical Science · doi:10.1042/cs20090313 · Cited by 79 · see citing works
Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients
Orellana, M. D., Rodrigo, R., Varela, N., Araya, J., PONIACHIK, J., Csendes, A., Smok, G., & Videla, L. A. (2005) · Hepatology Research · doi:10.1016/j.hepres.2005.10.001 · Cited by 78 · see citing works
Lycopene Prevents Development of Steatohepatitis in Experimental Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet
Bahçecioğlu, İ. H., Kuzu, N., Metin, K., Özercan, İ. H., Üstündağ, B., Şahin, K., & Küçük, Ö. (2010) · Veterinary Medicine International · doi:10.4061/2010/262179 · Cited by 75 · see citing works
Nonalcoholic fatty liver disease and type 2 diabetes: pathophysiological mechanisms shared between the two faces of the same coin
Acierno, C., Caturano, A., Pafundi, P. C., Nevola, R., Adinolfi, L. E., & Sasso, F. C. (2020) · Exploration of Medicine · doi:10.37349/emed.2020.00019 · Cited by 76 · see citing works
Metabolic dysfunction-associated steatotic liver disease-induced changes in the antioxidant system: a review
Svobodová, G., Horní, M., Velecká, E., & Boušová, I. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03889-x · Cited by 72 · see citing works
Mitochondria and Redox Signaling in Steatohepatitis
Morris, E. M., Rector, R. S., Thyfault, J. P., & Ibdah, J. A. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3795 · Cited by 71 · see citing works
Chronic oxidative stress sensitizes hepatocytes to death from 4-hydroxynonenal by JNK/c-Jun overactivation
Singh, R., Wang, Y., Schattenberg, J. M., Xiang, Y., & Czaja, M. J. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00151.2009 · Cited by 71 · see citing works
Impact of liver diseases on the development of type 2 diabetes mellitus
Hsieh, P. (2011) · World Journal of Gastroenterology · doi:10.3748/wjg.v17.i48.5240 · Cited by 68 · see citing works
Mitochondrial Reactive Oxygen Species Signal Hepatocyte Steatosis by Regulating the Phosphatidylinositol 3-Kinase Cell Survival Pathway
Kohli, R., Pan, X., Malladi, P., Wainwright, M. S., & Whitington, P. F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701759200 · Cited by 67 · see citing works
New insight and potential therapy for NAFLD: CYP2E1 and flavonoids
Wang, K., Tan, W., Liu, X., Deng, L., Huang, L., Wang, X., & Gao, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111326 · Cited by 67 · see citing works
Benzene Exposure Induces Insulin Resistance in Mice
Abplanalp, W. T., Wickramasinghe, N. S. M. D., Sithu, S. D., Conklin, D. J., Xie, Z., Bhatnagar, A., Srivastava, S., & O’Toole, T. E. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy252 · Cited by 64 · see citing works
Non-alcoholic Steatohepatitis in Children
Roberts, E. A. (2007) · Clinics in Liver Disease · doi:10.1016/j.cld.2007.02.008 · Cited by 64 · see citing works
Steatosis and NASH in type 2 diabetes
Hu, M., Phan, F., Bourron, O., Ferré, P., & Foufelle, F. (2017) · Biochimie · doi:10.1016/j.biochi.2017.10.019 · Cited by 63 · see citing works
Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates insulin resistance and hepatic steatosis via PI3K/Akt/GSK3β pathway
Zheng, X., Zhao, M., Jiang, C., Sheng, X., Yang, H., Liu, Y., Yao, X.-M., Zhang, J., & Yin, Z. (2019) · Phytomedicine · doi:10.1016/j.phymed.2019.153130 · Cited by 60 · see citing works
Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis
Chtioui, H., Semela, D., Ledermann, M., Zimmermann, A., & Dufour, J. (2007) · Liver International · doi:10.1111/j.1478-3231.2007.01524.x · Cited by 59 · see citing works
Overexpression of liver-specific cytochrome P4502E1 impairs hepatic insulin signaling in a transgenic mouse model of nonalcoholic fatty liver disease
Kathirvel, E., Morgan, K., French, S. W., & Morgan, T. R. M. (2009) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e328328f461 · Cited by 59 · see citing works
Insulin resistance in clinical and experimental alcoholic liver disease
Carr, R. M., & Correnti, J. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12787 · Cited by 56 · see citing works
Translational approaches: from fatty liver to non-alcoholic steatohepatitis.
Rosso, N., Chávez-Tapia, N. C., Tiribelli, C., & Bellentani, S. (2014) · PubMed Central · doi:10.3748/wjg.v20.i27.9038 · Cited by 56 · see citing works
Herbal Medicines for the Treatment of Nonalcoholic Steatohepatitis: Current Scenario and Future Prospects
Jadeja, R. N., Devkar, R., & Nammi, S. (2014) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2014/648308 · Cited by 55 · see citing works
Multi-technique comparison of atherogenic and MCD NASH models highlights changes in sphingolipid metabolism
Montandon, S. A., Somm, E., Loizides‐Mangold, U., Vito, C. D., Dibner, C., & Jornayvaz, F. R. (2019) · Scientific Reports · doi:10.1038/s41598-019-53346-4 · Cited by 55 · see citing works
The liver and the waistline: Fifty years of growth
Farrell, G. C. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2009.06080.x · Cited by 54 · see citing works
Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease
Sakurai, M., Takamura, T., Ota, T., Ando, H., Akahori, H., Kaji, K., Sasaki, M., Nakanuma, Y., Miura, K., & Kaneko, S. (2007) · Journal of Gastroenterology · doi:10.1007/s00535-006-1948- · Cited by 52 · see citing works
OSAS‐Related Inflammatory Mechanisms of Liver Injury in Nonalcoholic Fatty Liver Disease
Paschetta, E., Belci, P., Alisi, A., Liccardo, D., Cutrera, R., Musso, G., & Nobili, V. (2015) · Mediators of Inflammation · doi:10.1155/2015/815721 · Cited by 52 · see citing works
The Neuroprotective Role of Insulin Against MPP+‐Induced Parkinson's Disease in Differentiated SH‐SY5Y Cells
Ramalingam, M., & Kim, S. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25376 · Cited by 51 · see citing works
Cell death and nonalcoholic steatohepatitis: where is ballooning relevant?
Machado, M. V., & Cortez‐Pinto, H. (2011) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.11.16 · Cited by 50 · see citing works
NADPH oxidase is not an essential mediator of oxidative stress or liver injury in murine MCD diet-induced steatohepatitis
Peňa, A. D., Leclercq, I. A., Williams, J., & Farrell, G. C. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.08.025 · Cited by 50 · see citing works
New insights in the pathogenesis of non-alcoholic fatty liver disease
Gaemers, I. C., & Groen, A. K. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000226118.43178.98 · Cited by 49 · see citing works
Non-alcoholic fatty liver disease: From insulin resistance to mitochondrial dysfunction
Herruzo, J. A. S., Ruiz, I. G., Carreras, M. P., & Muñoz-Yagüe, M. T. (2006) · Revista Española de Enfermedades Digestivas · doi:10.4321/s1130-01082006001100006 · Cited by 48 · see citing works

Overexpression of liver-specific cytochrome P4502E1 impairs hepatic insulin signaling in a transgenic mouse model of nonalcoholic fatty liver disease
Kathirvel, E., Morgan, K., French, S. W., & Morgan, T. R. M. (2009) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e328328f461 · Cited by 59 · see citing works
CYP2E1-induzieter chronisch oxidativer Stress inhibiert Insulin Signaltransduktion in Hepatozyten
Schattenberg, J. M., Wang, Y., Rigoli, R. M., & Czaja, M. (2004) · Zeitschrift für Gastroenterologie · doi:10.1055/s-2004-831435
Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis
Abdelmegeed, M. A., Banerjee, A., Yoo, S.-H., Jang, S., Gonzalez, F. J., & Song, B. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.019 · Cited by 241 · see citing works
Effect of BI-1 on insulin resistance through regulation of CYP2E1
Lee, G., Oh, K., Kim, H., Han, H.-S., Lee, H.-Y., Park, K., Nam, K., Koo, S., & Chae, H. (2016) · Scientific Reports · doi:10.1038/srep32229 · Cited by 21 · see citing works
Increased insulin receptor substrate 2 expression is associated with steatohepatitis and altered lipid metabolism in obese subjects
Rametta, R., Mozzi, E., Dongiovanni, P., Motta, B. M., Milano, M., Roviaro, G., Fargion, S. R., & Valenti, L. V. C. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.181 · Cited by 43 · see citing works

Authors: Schattenberg, J. M., Wang, Y., Singh, R., Rigoli, R. M., & Czaja, M. J.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Czaja, Mark J.
ORCID: Schattenberg, Jörn M.
Wang, Yongjun
Singh, Rajat
Czaja, Mark J.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2005-03
Volume: 280
Issue: 11
Pages: 9887-9894
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m410310200
OpenAlex: W2070680921
Cited by: 194
References: 60
Citations by year: 2025: 1 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 12 · 2016: 13 · 2015: 11 · 2014: 12 · 2013: 8 · 2012: 8
FWCI: 15.06
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5707 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-61498, P30DK041296, DK41296, R01DK061498)
Topics: Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords: CYP2E1, insulin resistance, non-alcoholic fatty liver disease, steatohepatitis, IRS-1, insulin receptor substrate 2, Akt phosphorylation, glycogen synthase kinase-3, FOXO1, c-Jun N-terminal kinase, oxidative stress, methionine-choline-deficient diet
MeSH terms: Forkhead Box Protein O1, Adenoviridae, Animals, Cell Line, Choline, DNA-Binding Proteins, Fatty Liver, Glucose, Glutathione Peroxidase, Hepatitis, Humans, Insulin, Methionine, Mice, Inbred C57BL, Nerve Tissue Proteins, Phosphorylation, Proteins, Proto-Oncogene Proteins, RNA, Serine, Subcellular Fractions, Time Factors, Transcription Factors, Tyrosine, Blotting, Northern, Blotting, Western, Signal Transduction, Down-Regulation, Up-Regulation, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Cytochrome P-450 CYP2E1, Mitogen-Activated Protein Kinase Kinases, Hepatocytes, Glycogen Synthase Kinase 3, Immunoprecipitation, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Proto-Oncogene Proteins c-akt, Mice, Rats, Forkhead Transcription Factors

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Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling

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