Fig. 5. Dysregulated cell senescence and fatty acid metabolism in Acss1^K635Q/K635Q liver.

(A) Total RNAs were isolated from the liver tissues of wild-type and Acss1^K635Q/K635Q mice after a 48-hour fast and sent for RNA-seq (N = 3 mice per group). Differentially expressed genes were processed using the Qiagen Ingenuity Pathway Analysis (IPA) software to determine pathway enrichment and significance scores. Bar graph shows the top five differentially regulated Ingenuity Canonical Pathways by P value as well as select differentially regulated pathways involved in metabolism and stress response. Venn diagram shows overlap between differentially regulated genes involved in hepatic steatosis and cellular senescence. (B and C) Immunoblots showing relative p53, p21, and SA-β-gal levels in liver tissue from (B) fasted and (C) fed wild-type and Acss1^K635Q/K635Q mice. (D) IHC staining for SA-β-gal in liver tissue from fed and fasted wild-type and Acss1^K635Q/K635Q mice. Scale bars, 100 μm.