C/EBP homologous protein modulates liraglutide-mediated attenuation of non-alcoholic steatohepatitis

Rahman, Khalidur; Liu, Yunshan; Kumar, Pradeep; Smith, Tekla; Thorn, Natalie E; Farris, Alton B; Anania, Frank A

doi:10.1038/labinvest.2016.61

Cited by 39Liver Disease Diagnosis and TreatmentEndoplasmic Reticulum Stress and DiseaseLiver physiology and pathology

C/EBP homologous protein modulates liraglutide-mediated attenuation of non-alcoholic steatohepatitis

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Rahman, Khalidur, Liu, Yunshan, Kumar, Pradeep, Smith, Tekla, Thorn, Natalie E, Farris, Alton B, Anania, Frank A·2016·Laboratory Investigation

DOI 10.1038/labinvest.2016.61PMC PMC4965279

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Abstract

The CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), a major transcriptional regulator of endoplasmic reticulum (ER) stress-mediated apoptosis, is implicated in lipotoxicity-induced ER stress and hepatocyte apoptosis in non-alcoholic fatty liver disease (NAFLD). We have previously demonstrated that the glucagon-like peptide-1 (GLP-1) agonist, liraglutide, protects steatotic hepatocytes from lipotoxicity-induced apoptosis by improved handling of free fatty acid (FFA)-induced ER stress. In the present study, we investigated whether CHOP is critical for GLP-1-mediated restoration of ER homeostasis and mitigation of hepatocyte apoptosis in a murine model of NASH (non-alcoholic steatohepatitis). Our data show that despite similar caloric intake, CHOP KO (CHOP(-/-)) mice fed a diet high in fat, fructose, and cholesterol (HFCD) for 16 weeks developed more severe histological features of NASH compared with wild-type (WT) controls. Severity of NASH in HFCD-fed CHOP(-/-) mice correlated with significant decrease in peroxisomal β-oxidation, and increased de novo lipogenesis and ER stress-mediated hepatocyte apoptosis. Four weeks of liraglutide treatment markedly attenuated steatohepatitis in HFCD-fed WT mice by improving insulin sensitivity, and suppressing de novo lipogenesis and ER stress-mediated hepatocyte apoptosis. However, in the absence of CHOP, liraglutide did not improve insulin sensitivity, nor suppress peroxisomal β-oxidation or ER stress-mediated hepatocyte apoptosis. Taken together, these data indicate that CHOP protects hepatocytes from HFCD-induced ER stress, and has a significant role in the mechanism of liraglutide-mediated protection against NASH pathogenesis.

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Mechanisms of lysosomal degradation and autophagy are crucial to remove potentially toxic and protective fatty acids against ER stress-induced cell death.
“The mechanisms of lysosomal degradation and autophagy are crucial to remove potentially toxic and protective fatty acids against ER stress-induced cell death [129,130,131].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [131]

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Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638 · see citing works
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791 · see citing works
Self-citation
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Walter, P., & Ron, D. (2011) · Science · doi:10.1126/science.1209038 · Cited by 5,893 · see citing works
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Adams, L. A., Lymp, J. F., St. Sauver, J., Sanderson, S. O., Lindor, K. D., Feldstein, A., & Angulo, P. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.014 · Cited by 2,890 · see citing works
Roles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,833 · see citing works
Mediators of endoplasmic reticulum stress-induced apoptosis
Szegezdi, E., Logue, S. E., Gorman, A. M., & Samali, A. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400779 · Cited by 2,345 · see citing works
Endoplasmic reticulum stress: cell life and death decisions
Xu, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26373 · Cited by 2,260 · see citing works
Prevalence of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among a Largely Middle-Aged Population Utilizing Ultrasound and Liver Biopsy: A Prospective Study
Williams, C. D., Stengel, J. Z., Asike, M., Torres, D. M., Shaw, J. C., Contreras, M., Landt, C. L., & Harrison, S. A. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.09.038 · Cited by 2,146 · see citing works
Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score and the Histopathologic Diagnosis in NAFLD: Distinct Clinicopathologic Meanings §Δ
Brunt, E. M., Kleiner, D. E., Wilson, L. A., Belt, P., & Neuschwander-Tetri, B. A. (2011) · Hepatology · doi:10.1002/hep.24127 · Cited by 1,251 · see citing works
Endoplasmic reticulum stress in liver disease
Malhi, H., & Kaufman, R. J. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.11.005 · Cited by 1,178 · see citing works
Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites†
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077 · see citing works
Targeted disruption of the Chop gene delays endoplasmic reticulum stress–mediated diabetes
Oyadomari, S., Koizumi, A., Takeda, K., Gotoh, T., Akira, S., Araki, E., & Mori, M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14550 · Cited by 858 · see citing works
Targeted disruption of the chop gene delays endoplasmic reticulum stress-mediated diabetes
Oyadomari, S., Koizumi, A., Takeda, K., Gotoh, T., Akira, S., Araki, E., & Mori, M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214550 · Cited by 752 · see citing works
Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes
Song, B., Scheuner, D. L., Ron, D., Pennathur, S., & Kaufman, R. J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34587 · Cited by 693 · see citing works
Endoplasmic reticulum stress, obesity and diabetes.
Cnop, M., Foufelle, F., & Velloso, L. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.07.010 · Cited by 660 · see citing works
From NAFLD to NASH to cirrhosis—new insights into disease mechanisms
Wree, A., Broderick, L., Canbay, A. E., Hoffman, H. M., & Feldstein, A. E. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.149 · Cited by 608 · see citing works
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Rutkowski, D. T., Wu, J., Back, S.-H., Callaghan, M. U., Ferris, S. P., Iqbal, J., Clark, R. L., Miao, H. Z., Hassler, J. R., Fornek, J. L., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.10.015 · Cited by 580 · 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
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Gupta, N. A., Mells, J., Dunham, R. M., Grakoui, A., Handy, J., Saxena, N. K., & Anania, F. A. (2010) · Hepatology · doi:10.1002/hep.23569 · Cited by 532 · see citing works
Self-citation
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Wang, D., Wei, Y., & Pagliassotti, M. J. (2005) · Endocrinology · doi:10.1210/en.2005-0570 · Cited by 529 · see citing works
New insights into the roles of CHOP-induced apoptosis in ER stress
Li, Y., Guo, Y., Tang, J., Jiang, J., & Chen, Z. (2014) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmu048 · Cited by 529 · see citing works
Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response
Okada, T., Yoshida, H., Akazawa, R., Negishi, M., & Mori, K. (2002) · Biochemical Journal · doi:10.1042/bj20020391 · Cited by 522 · see citing works
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis
Armstrong, M. J., Hull, D., Guo, K., Barton, D., Hazlehurst, J. M., Gathercole, L. L., Nasiri, M., Yu, J., Gough, S. C., Newsome, P. N., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.038 · Cited by 456 · see citing works
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Tetri, L. H., Başaranoğlu, M., Brunt, E. M., Yerian, L. M., & Neuschwander‐Tetri, B. A. (2008) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.90272.2008 · Cited by 448 · see citing works
Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition
Charlton, M., Krishnan, A., Viker, K., Sanderson, S. O., Cazanave, S. C., McConico, A. L., Masuoko, H., & Gores, G. J. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00145.2011 · Cited by 444 · see citing works
Dephosphorylation of Translation Initiation Factor 2α Enhances Glucose Tolerance and Attenuates Hepatosteatosis in Mice
Oyadomari, S., Harding, H. P., Zhang, Y., Oyadomari, M., & Ron, D. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.011 · Cited by 431 · see citing works
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Drucker, D. J. (2001) · Endocrinology · doi:10.1210/endo.142.2.7983 · Cited by 421 · see citing works
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Thorp, E. B., Li, G., Seimon, T. A., Kuriakose, G., Ron, D., & Tabas, I. A. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.003 · Cited by 342 · see citing works
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Silva, R. M., Ries, V., Oo, T. F., Yarygina, O., Jackson-Lewis, V. R., Ryu, E. J., Lu, P. D., Marciniak, S. J., Ron, D., Przedborski, S., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03428.x · Cited by 285 · see citing works
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Li, Y., Ge, M., Ciani, L., Kuriakose, G., Westover, E. J., Důra, M., Covey, D. F., Freed, J. H., Maxfield, F. R., Lytton, J., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405195200 · Cited by 282 · see citing works
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Self-citation
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Li, J., Huang, J., Li, J.-S., Chen, H., Huang, K., & Zheng, L. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2011.10.018 · Cited by 168 · see citing works
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Malhi, H., Kropp, E. M., Clavo, V., Kobrossi, C. R., Han, J., Mauer, A. S., Yong, J., & Kaufman, R. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442954 · Cited by 86 · see citing works
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Yang, M., Zhang, D., Zhao, Z., Sit, J., Saint-Sume, M., Shabandri, O., Zhang, K., Yin, L., & Tong, X. (2020) · The FASEB Journal · doi:10.1096/fj.201903292rr · Cited by 29 · see citing works
Glycine‐β‐muricholic acid antagonizes the intestinal farnesoid X receptor–ceramide axis and ameliorates NASH in mice
Jiang, J., Ma, Y., Liu, Y., Lu, D., Gao, X., Krausz, K. W., Desai, D. H., Amin, S., Patterson, A. D., Gonzalez, F. J., et al. (2022) · Hepatology Communications · doi:10.1002/hep4.2099 · Cited by 27 · see citing works
Self-citation
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Lee, Y. S., Riopel, M., Cabrales, P., & Bandyopadhyay, G. K. (2019) · Science Advances · doi:10.1126/sciadv.aaw4176 · Cited by 30 · see citing works
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Guo, Q., Xin, M., Lu, Q., Feng, D., Yang, V., Peng, L. F., Whelan, K. A., Hu, W., Wu, S. L., Yang, X., et al. (2023) · Theranostics · doi:10.7150/thno.81192 · Cited by 27 · see citing works
Role of the inflammasome, gasdermin D, and pyroptosis in non‐alcoholic fatty liver disease
Rodríguez‐Antonio, I., López-Sánchez, G. N., Uribe, M., Chávez-Tapia, N. C., & Nuño‐Lámbarri, N. (2021) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15561 · Cited by 24 · see citing works
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Chen, Q., Fang, W., Cui, K., Chen, Q., Xiang, X., Zhang, J., Zhang, Y., Mai, K., & Ai, Q. (2021) · The FASEB Journal · doi:10.1096/fj.202100739rr · Cited by 23 · see citing works
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Targeting incretin hormones and the ASK-1 pathway as therapeutic options in the treatment of non-alcoholic steatohepatitis
Kovalic, A. J., Satapathy, S. K., & Chalasani, N. (2018) · Hepatology International · doi:10.1007/s12072-018-9854-1 · Cited by 22 · see citing works
Pectic oligosaccharides ameliorate high-fat diet-induced obesity and hepatic steatosis in association with modulating gut microbiota in mice
Yu, S., Wang, H., Cui, L., Wang, J., Zhang, Z., Wu, Z., Lin, X., He, N., Zou, Y., & Li, S. (2023) · Food & Function · doi:10.1039/d3fo02168h · Cited by 21 · see citing works
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ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets
Duwaerts, C. C., & Maiers, J. L. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.804097 · Cited by 16 · see citing works
Potentilla anserina L. attenuates oleic acid-induced steatosis in HepG2 cells and hyperlipidemia in high fat diet-induced obese mice
Yan, Y., & Zhang, W. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105772 · Cited by 7 · see citing works
Meta-analysis of the clinical efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease
Xu, Y., Wang, X., She, Y., Liu, J., & Zhang, Q. (2024) · Endocrine Journal · doi:10.1507/endocrj.ej24-0168 · Cited by 6 · see citing works
Effect of glucagon-like peptide-1 receptor agonists on adipokine level of nonalcoholic fatty liver disease in rats fed high-fat diet
Jin, M., Niu, X., Liu, Y., Zhang, D., Yuan, D., & Shen, H. (2020) · Open Medicine · doi:10.1515/med-2020-0212 · Cited by 4 · see citing works
Self-citation
Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation
Li, Y., Zheng, J., He, P., Cai, X. L., Pan, X., Li, H. Q., Hong, Q., Hu, Z. J., Wu, Y., & Peng, X. (2021) · BMC Gastroenterology · doi:10.1186/s12876-021-01750-4 · Cited by 3 · see citing works
Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLDPreprint
Park, S., Helsley, R. N., Fadhul, T., Willoughby, J. L. S., Noetzli, L. J., Tu, H.-C., Solheim, M. H., Fujisaka, S., Pan, H., Dreyfuss, J. M., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.27.525605 · Cited by 3 · see citing works
Efficacy and safety of liraglutide in non‐alcoholic fatty liver disease with or without type 2 diabetes: A systematic review and meta‐analysis
Kong, W., Fang, B., & Xing, W. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70301 · Cited by 2 · see citing works
Targeting ER Stress of GLP-1 Receptor Agonist in Diabetic Retinopathy
Huang, H., Wang, Y., Gao, S., Li, N., Zhong, Y., & Shen, X. P. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117623 · Cited by 1 · see citing works
Effect of Incretogenic Peptides on Non-Alcoholic Fatty Liver Disease
苏, 怡. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.1361396
Additional file 1 of Identifying potential biomarkers of nonalcoholic fatty liver disease via genome-wide analysis of copy number variation
Li, Y. F., Zheng, J., Peng, H. W., Cai, X. L., Pan, X., Li, H. Q., Hong, Q. Z., Hu, Z. J., Wu, Y. L., & Peng, X.-E. (2021) · Figshare · doi:10.6084/m9.figshare.14418098

Glucagon‐like peptide‐1 preserves non‐alcoholic fatty liver disease through inhibition of the endoplasmic reticulum stress‐associated pathway
Ao, N., Yang, J., Wang, X., & Du, J. (2016) · Hepatology Research · doi:10.1111/hepr.12551 · Cited by 56 · see citing works
C/EBP Homologous Protein-induced Macrophage Apoptosis Protects Mice from Steatohepatitis
Malhi, H., Kropp, E. M., Clavo, V., Kobrossi, C. R., Han, J., Mauer, A. S., Yong, J., & Kaufman, R. J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442954 · Cited by 86 · see citing works
The influence of liraglutide on ERp46 in non-alcoholic fatty liver disease rats
Ao, N., Yang, J., Zheng, L., & Ma, J. (2018) · Zhonghua neifenmi daixie zazhi · doi:10.3760/cma.j.issn.1000-6699.2018.02.010 · Cited by 1 · see citing works
GLP-1 Analogs Reduce Hepatocyte Steatosis and Improve Survival by Enhancing the Unfolded Protein Response and Promoting Macroautophagy
Sharma, S., Mells, J. E., Fu, P. P., Saxena, N. K., & Anania, F. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025269 · Cited by 272 · see citing works
Self-citation
Effective treatment for fatty liver of liraglutide via inhibiting endoplasmic reticulum stress, oxidative stress and apoptosis pathways
Li, J., Xu, J., Zhu, F., & Wang, C. (2024) · Archives of Medical Science · doi:10.5114/aoms/186658

Authors: Rahman, K., Liu, Y., Kumar, P., Smith, T., Thorn, N. E., Farris, A. B., & Anania, F. A.
Affiliations: Emory University (US)
Atlanta VA Medical Center (US)
Emory University Hospital (US)
Corresponding author: Rahman, Khalidur
ORCID: Rahman, Khalidur
Liu, Yunshan
Kumar, Pradeep
Farris, Alton B
Anania, Frank A
Venue: Laboratory Investigation
Publisher: Elsevier BV
Published: 2016-08
Volume: 96
Issue: 8
Pages: 895-908
ISSN: 0023-6837 (ISSN-L)
DOI: 10.1038/labinvest.2016.61
PMC: PMC4965279
OpenAlex: W2413093647
Cited by: 39
References: 53
Citations by year: 2025: 2 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 1
FWCI: 4.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2354 d)
Locations: Laboratory Investigation (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX001746)
Emory University
National Institutes of Health (DK062092)
School of Medicine, Emory University
National Institute of Diabetes and Digestive and Kidney Diseases (R56DK062092, R01DK062092)
Topics: Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: CHOP, C/EBP homologous protein, liraglutide, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, endoplasmic reticulum stress, hepatocyte apoptosis, lipotoxicity, GLP-1 receptor agonists, peroxisomal beta-oxidation, de novo lipogenesis, insulin sensitivity, ER homeostasis
MeSH terms: Liraglutide, Exenatide, Animals, Blood Glucose, Cells, Cultured, Cholesterol, Dietary Carbohydrates, Disease Models, Animal, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Peptides, Venoms, Apoptosis, Mice, Knockout, Protective Agents, Hepatocytes, Lipid Metabolism, Mice, Transcription Factor CHOP, Diet, High-Fat, Endoplasmic Reticulum Stress, Non-alcoholic Fatty Liver Disease

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C/EBP homologous protein modulates liraglutide-mediated attenuation of non-alcoholic steatohepatitis

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