Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice
Open accessAbstract
The prevalence of non-alcoholic steatohepatitis (NASH) rapidly increases with metabolic disorders such as dyslipidaemia, high blood pressure, and hyperglycaemia. B cell lymphoma 6 (Bcl6), a transcriptional repressor, is essential for the formation of germinal centre B cells. In this study, we analysed the role of Bcl6 in NASH progression-associated pathological changes, such as hepatic lipid accumulation, liver fibrosis, and hepatocarcinogenesis. The roles of Bcl6 in NASH were analysed using liver-specific Bcl6 knockout (Bcl6-LKO) and control wild-type (WT) mice. The murine NASH model was established by feeding the mice with choline-deficient, L-amino-acid-defined, high-fat diet (CDAHFD). Feeding the WT mice with CDAHFD for 7 weeks induced the formation of histopathological features resembling human NASH, such as hepatic lipid accumulation, hepatocellular injury, and fibrosis. These histopathological changes were significantly attenuated in Bcl6-LKO mice. Additionally, feeding the male WT mice with CDAHFD for 38 weeks induced the formation of liver tumours, which was suppressed in Bcl6-LKO mice. These findings indicate that Bcl6 is involved in the progression of NASH and NASH-derived tumours.
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Bcl6 is a transcriptional repressor that is enriched in the fed state and cooperates with PPARα to suppress the induction of fasting transcription, and Bcl6 loss has been shown to increase insulin sensitivity and repress NASH.
“Bcl6 is a transcriptional repressor that is enriched in the fed state and cooperates with PPARα to suppress the induction of fasting transcription, and Bcl6 loss has been shown to increase insulin sensitivity and repress NASH36-38.”
From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [37]
The Introduction identifies Bcl6 as a transcriptional repressor, and the Abstract reports that liver-specific Bcl6 knockout attenuated NASH-like changes in mice fed a CDAHFD diet. The Introduction says only that prior work found Bcl6 regulates insulin sensitivity; it does not state the direction of the effect. Our copy does not establish enrichment in the fed state or cooperation with PPARα to suppress fasting transcription. Page numbers were not available in the indexed passages. (LLM, conf=0.88)
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Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285 · see citing works
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548 · see citing works
Non-alcoholic fatty liver disease - a global public health perspective
Younossi, Z. M. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.033 · Cited by 2,149 · see citing works
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M. (2007) · Science · doi:10.1126/science.1140485 · Cited by 1,955 · see citing works
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Postic, C., Shiota, M., Niswender, K. D., Jetton, T. L., Chen, Y., Moates, J. M., Shelton, K. D., Lindner, J., Cherrington, A. D., & Magnuson, M. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.1.305 · Cited by 1,302 · see citing works
Control of Inflammation, Cytokine Expression, and Germinal Center Formation by BCL-6
Dent, A. L., Shaffer, A. L., Yu, X., Allman, D., & Staudt, L. M. (1997) · Science · doi:10.1126/science.276.5312.589 · Cited by 945 · see citing works
León, A. L.-D., & Rojkind, M. (1985) · Journal of Histochemistry & Cytochemistry · doi:10.1177/33.8.2410480 · Cited by 607 · see citing works
A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer
Asgharpour, A., Cazanave, S. C., Pacana, T., Seneshaw, M., Vincent, R., Banini, B. A., Kumar, D. P., Daita, K., Min, H.-K., Mirshahi, F., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.05.005 · Cited by 538 · 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
Liver-Specific Inhibition of ChREBP Improves Hepatic Steatosis and Insulin Resistance in ob/ob Mice
Dentin, R., Benhamed, F., Hainault, I., Fauveau, V., Foufelle, F., Dyck, J. R. B., Girard, J. R., & Postic, C. (2006) · Diabetes · doi:10.2337/db06-0200 · Cited by 429 · see citing works
Kerckaert, J., Deweindt, C., Tilly, H., Quief, S., Lecocq, G., & Bastard, C. (1993) · Nature Genetics · doi:10.1038/ng0993-66 · Cited by 426 · see citing works
A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo
Cerchietti, L. C., Ghetu, A. F., Zhu, X., Da Silva, G. F., Zhong, S., Matthews, M., Bunting, K. L., Polo, J. M., Farès, C., Arrowsmith, C. H., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.050 · Cited by 288 · see citing works
Kaji, T., Ishige, A., Hikida, M., Taka, J., Hijikata, A., Kubo, M., Nagashima, T., Takahashi, Y., Kurosaki, T., Okada, M., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120127 · Cited by 263 · see citing works
Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?
Febbraio, M. A., Reibe, S., Shalapour, S., Ooi, G., Watt, M. J., & Karin, M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.10.012 · Cited by 250 · see citing works
Wolska, A., Dunbar, R. L., Freeman, L. A., Ueda, M., Amar, M. J., Sviridov, D. O., & Remaley, A. T. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.025 · Cited by 231 · see citing works
Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6
Kerres, N., Steurer, S., Schlager, S., Bader, G., Berger, H., Caligiuri, M., Dank, C., Engen, J. R., Ettmayer, P., Fischerauer, B., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.081 · Cited by 207 · see citing works
Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma
Cardenas, M. G., Yu, W., Beguelin, W., Teater, M. R., Geng, H., Goldstein, R. L., Oswald, E., Hatzi, K., Yang, S.-N., Cohen, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85795 · Cited by 176 · see citing works
Ikawa‐Yoshida, A., Matsuo, S., Kato, A., Ohmori, Y., Higashida, A., Kaneko, E., & Matsumoto, M. (2017) · International Journal of Experimental Pathology · doi:10.1111/iep.12240 · Cited by 98 · see citing works
A critical review of endpoints for non-cirrhotic NASH therapeutic trials
Ratziu, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.12.001 · Cited by 74 · see citing works
The role of Bcl6 in mature cardiac myocytes
Yoshida, T. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00007-3 · Cited by 69 · see citing works
Dynamic repression by BCL6 controls the genome-wide liver response to fasting and steatosis
Sommars, M. A., Ramachandran, K., Senagolage, M. D., Futtner, C. R., Germain, D. M., Allred, A. L., Omura, Y., Bederman, I. R., & Barish, G. D. (2019) · eLife · doi:10.7554/elife.43922 · Cited by 66 · see citing works
Influence of age and gender in Japanese patients with non‐alcoholic steatohepatitis
Yatsuji, S., Hashimoto, E., Tobari, M., Tokushige, K., & Shiratori, K. (2007) · Hepatology Research · doi:10.1111/j.1872-034x.2007.00156.x · Cited by 57 · see citing works
Current and emerging pharmacological therapy for non-alcoholic fatty liver disease
Eshraghian, A. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i42.7495 · Cited by 51 · see citing works
Loss of transcriptional repression by BCL6 confers insulin sensitivity in the setting of obesity
Senagolage, M. D., Sommars, M. A., Ramachandran, K., Futtner, C. R., Omura, Y., Allred, A. L., Wang, J., Yang, C., Procissi, D., Evans, R. M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.074 · Cited by 44 · see citing works
Takakura, K., Oikawa, T., Nakano, M., Saeki, C., Torisu, Y., Kajihara, M., & Saruta, M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00762 · Cited by 40 · see citing works
Rangnekar, A. S., Lammert, F., Igolnikov, A., & Green, R. M. (2006) · Liver International · doi:10.1111/j.1478-3231.2006.01314.x · Cited by 38 · see citing works
LaPensee, C. R., Lin, G., Dent, A. L., & Schwartz, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097090 · Cited by 37 · see citing works
Transgenic expression of osteoactivin in the liver attenuates hepatic fibrosis in rats
Abe, H., Uto, H., Takami, Y., Takahama, Y., Hasuike, S., Kodama, M., Nagata, K., Moriuchi, A., Numata, M., Ido, A., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.03.035 · Cited by 37 · see citing works
Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?
Meringer, H., Shibolet, O., & Deutsch, L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i29.3929 · Cited by 36 · see citing works
Chikada, H., Ida, K., Ando, E., Inagaki, Y., Sakamoto, A., & Kamiya, A. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0088-6 · Cited by 31 · see citing works
Self-citationGender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1
Matsushita, N., Hassanein, M. T., Martínez‐Clemente, M., Lazaro, R. G., French, S. W., Xie, W., Lai, K. K. Y., Karin, M., & Tsukamoto, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181052 · Cited by 26 · see citing works
Sameshima, T., Yamamoto, T., Sano, O., Sogabe, S., Igaki, S., Sakamoto, K., Ida, K., Gotou, M., Imaeda, Y., Sakamoto, J., et al. (2018) · Biochemistry · doi:10.1021/acs.biochem.7b00732 · Cited by 23 · see citing works
Self-citationNiwa‐Kawakita, M., Abramowski, V., Kalamarides, M., Thomas, G. D., & Giovannini, M. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 22 · see citing works
Shi, T., Yang, X., Zhou, H., Xi, J., Sun, J., Ke, Y., Zhang, J., Shao, Y., Jiang, X., Pan, X., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0189856 · Cited by 19 · see citing works
Flagged first, then by citations
1 of the 37 references couldn’t be matched to a known paper.
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Sorted by citations
Nalkurthi, C., Schroder, W. A., Melino, M., Irvine, K. M., Nyuydzefe, M., Chen, W., Liu, J., Teng, M. W. L., Hill, G. R., Bertolino, P., et al. (2022) · JHEP Reports · doi:10.1016/j.jhepr.2021.100386 · Cited by 75 · see citing works
Wang, Z., Zhu, S., Jia, Y., Wang, Y., Kubota, N., Fujiwara, N., Gordillo, R., Lewis, C., Zhu, M., Sharma, T., et al. (2023) · Cell · doi:10.1016/j.cell.2023.03.014 · Cited by 72 · see citing works
Liver-specific actions of GH and IGF1 that protect against MASLD
Kineman, R. D., del Río-Moreno, M., & Waxman, D. J. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01037-0 · Cited by 39 · see citing works
Zhang, H., Li, Y., Zhang, C., Huang, K., Zhao, J., Le, S., Jiang, L., Liu, H., Yang, P., Xiao, X., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04812-x · Cited by 25 · see citing works
Bioinformatic Analysis of Crosstalk Between circRNA, miRNA, and Target Gene Network in NAFLD
Du, C., Shen, L., Ma, Z., Du, J., & Jin, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.671523 · Cited by 14 · see citing works
Li, J., Feng, J., Li, Z., Ni, Y., Liu, L., Xia, L., Chai, Z., Zhuang, N., Xu, J., He, Y., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00625-7 · Cited by 12 · see citing works
Deletion of Jazf1 gene causes early growth retardation and insulin resistance in mice
Lee, H., Jang, H. R., Li, H., Samuel, V. T., Dudek, K. D., Osipovich, A. B., Magnuson, M. A., Sklar, J., & Shulman, G. I. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2213628119 · Cited by 12 · see citing works
Zhang, Z., Li, J., Ma, M., Shi, H., Lu, M., Liang, F., Wang, X., Ma, P., Tian, Y., Song, D., et al. (2024) · Talanta · doi:10.1016/j.talanta.2024.127378 · Cited by 9 · see citing works
Du, M., Li, X., Xiao, F., Fu, Y., Shi, Y., Guo, S., Chen, L., Shen, L., Wang, L., Cheng, H., et al. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155244 · Cited by 7 · see citing works
BCL6 coordinates muscle mass homeostasis with nutritional states
Wang, H. J., Fan, W., Liu, S., Kim, K., Matsushima, A., Ogawa, S., Kang, H. G., Zhu, J., Estepa, G., He, M., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2408896122 · Cited by 6 · see citing works
Iannone, V., Vaittinen, M., Gómez-Gallego, C., Mikkonen, S. J., Lok, J., D’Auria, G., Vazquez-Uribe, R., Tikkanen, I., Sommer, M. O. A., El-Nezami, H. S., et al. (2025) · International Journal of Obesity · doi:10.1038/s41366-025-01774-w · Cited by 6 · see citing works
Kamiya, A., & Ida, K. (2022) · Cells · doi:10.3390/cells11233751 · Cited by 3 · see citing works
Self-citationZhang, J., Zhao, Y., Pulivendala, G., Zhang, Q., Rui, L., Gao, J., Wang, H., Zhang, G., Nuotio-Antar, A. M., Tong, X., et al. (2025) · Advanced Science · doi:10.1002/advs.202415032 · Cited by 1 · see citing works
Han, H., Li, Q., Wang, C., Liang, Z., Zhang, L., Zhang, S., Tian, M., Li, S., Liu, D., Yang, G., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.07.028 · Cited by 1 · see citing works
Prevention of Cholestatic Liver Disease Through BCL6-FXR Enterohepatic Crosstalk
Fruzyna, E., Sommars, M. A., Omura, Y., Yarnoff, K. M., Wang, J. C., Futtner, C. R., Green, R. M., & Barish, G. D. (2025) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2025.101706 · Cited by 1 · see citing works
The DNA binding protein BCL6 regulates NFκB-controlled endothelial inflammatory gene expressionPreprint
Acevedo, A. F., Mack, J. J., & Valenzuela, N. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.03.514942 · Cited by 1 · see citing works
Cheng, Q., Li, J., Feng, J., Li, Z., Ni, Y., Liu, L., Xia, L., Chai, Z., Zhuang, N., Xu, J., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3566958/v1
- Authors
- Chikada, H., Ida, K., Nishikawa, Y., Inagaki, Y., & Kamiya, A.
- Affiliations
- Tokai University (JP)
- Asahikawa Medical University (JP)
- Corresponding author
- Kamiya, Akihide
- Venue
- Scientific Reports
- Published
- 2020-06-16
- Volume
- 10
- Issue
- 1
- Pages
- 9704-9704
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7297717
- OpenAlex
- W3035322654
- Cited by
- 17
- References
- 37
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 2
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (19H03448, 18J40228, 19H03643, 17H04166, 19K22627)
- 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
- BCL6, nonalcoholic steatohepatitis, liver-specific knockout, hepatic lipid accumulation, liver fibrosis, hepatocarcinogenesis, hepatic steatosis, transcriptional repressor
- MeSH terms
- Animals, Disease Models, Animal, Female, Liver, Male, Triglycerides, Mice, Knockout, Disease Progression, Lipid Metabolism, Mice, Proto-Oncogene Proteins c-bcl-6, Real-Time Polymerase Chain Reaction, Non-alcoholic Fatty Liver Disease
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