Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice

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 analys...

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Bibliographic Details
Published in:Scientific reports 2020-06, Vol.10 (1), p.9704-9704, Article 9704
Main Authors: Chikada, Hiromi, Ida, Kinuyo, Nishikawa, Yuji, Inagaki, Yutaka, Kamiya, Akihide
Format: Article
Language:English
Subjects:
692/4020/4021/1607/2750
692/4020/4021/1607/2751
Animals
Bcl-6 protein
Blood pressure
Choline
Disease Models, Animal
Disease Progression
Dyslipidemia
Female
Fibrosis
High fat diet
Humanities and Social Sciences
Hyperglycemia
Hypertension
Lipid Metabolism
Liver
Liver - chemistry
Liver - metabolism
Lymphocytes B
Lymphoma
Male
Metabolic disorders
Mice
Mice, Knockout
multidisciplinary
Non-alcoholic Fatty Liver Disease - etiology
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Nutrient deficiency
Proto-Oncogene Proteins c-bcl-6 - metabolism
Proto-Oncogene Proteins c-bcl-6 - physiology
Real-Time Polymerase Chain Reaction
Science
Science (multidisciplinary)
Transcription
Triglycerides - analysis
Triglycerides - metabolism
Tumors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-66539-z