Gender differences in diet-induced steatotic disease in Cyp2b-null mice

PloS One
Melissa M HeintzWilliam S Baldwin

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease; however, progression to nonalcoholic steatohepatitis (NASH) is associated with most adverse outcomes. CYP2B metabolizes multiple xeno- and endobiotics, and male Cyp2b-null mice are diet-induced obese (DIO) with increased NAFLD. However, the DIO study was not performed long enough to assess progression to NASH. Therefore, to assess the role of Cyp2b in fatty liver disease progression from NAFLD to NASH, we treated wildtype (WT) and Cyp2b-null mice with a normal diet (ND) or choline-deficient, L-amino acid-defined high fat diet (CDAHFD) for 8 weeks and determined metabolic and molecular changes. CDAHFD-fed WT female mice gained more weight and had greater liver and white adipose tissue mass than their Cyp2b-null counterparts; males experienced diet-induced weight loss regardless of genotype. Serum biomarkers of liver injury increased in both CDAHFD-fed female and male mice; however CDAHFD-fed Cyp2b-null females exhibited significantly lower serum ALT, AST, and ASP concentrations compared to WT mice, indicating Cyp2b-null females were protected from liver injury. In both genders, hierarchical clustering of RNA-seq data demonstrates several gene ontologies r...Continue Reading

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Citations

Mar 20, 2021·Antioxidants & Redox Signaling·Andrea Morán-CostoyaAdamo Valle
Oct 10, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Na YangYu-Bo Li
Apr 11, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Matthew C HamiltonWilliam S Baldwin

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Methods Mentioned

BETA
RNAseq
RNA-seq

Software Mentioned

FastQC
R
Trimmomatic
GSNAP
GraphPad
GOSeq
EdgeR
Graphpad Prism
Revigo
KEGG Mapper

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