RRC ID 60829
Author Chikada H, Ida K, Nishikawa Y, Inagaki Y, Kamiya A.
Title Liver-specific knockout of B cell lymphoma 6 suppresses progression of non-alcoholic steatohepatitis in mice.
Journal Sci Rep
Abstract 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.
Volume 10(1)
Pages 9704
Published 2020-6-16
DOI 10.1038/s41598-020-66539-z
PII 10.1038/s41598-020-66539-z
PMID 32546802
PMC PMC7297717
MeSH Animals Disease Models, Animal Disease Progression Female Lipid Metabolism Liver / chemistry Liver / metabolism* Male Mice Mice, Knockout Non-alcoholic Fatty Liver Disease / etiology Non-alcoholic Fatty Liver Disease / metabolism Non-alcoholic Fatty Liver Disease / pathology* Proto-Oncogene Proteins c-bcl-6 / metabolism* Proto-Oncogene Proteins c-bcl-6 / physiology Real-Time Polymerase Chain Reaction Triglycerides / analysis Triglycerides / metabolism
IF 4.011
Mice RBRC05663