Fig. 3: Spontaneous steatosis in hepatocyte-specific Usp39 knockout mice.

a Representative liver and spleen images from 12-month-old male mice fasted for 16 h. b H&E staining and Sirius Red staining of liver sections in 12-month-old male mice (n = 3 per group). Scale bars, 50 µm. c Hepatic TG levels were analyzed in 12-month-old male mice fasted for 16 h (n = 8 per group). d qPCR was performed to analyze mRNA expression of indicated genes in livers of 12-month-old male mice (n = 3). e Representative liver images from control and Usp39-HKO male mice fed the HFD for 12 weeks. f H&E (left), Oil Red O (middle), and Sirius Red staining (right) of liver sections from 16-week-old male mice fed the HFD for 12 weeks (n = 3). Scale bars, 50 µm. g Hepatic TG levels were analyzed in16-week-old male mice fed the HFD for 12 weeks (n = 3). h qPCR was performed to analyze mRNA expression of indicated genes in livers of control and Usp39-HKO male mice fed the HFD for 12 weeks (n = 3). i Heatmap showing lipidomic data in the livers of 5-week-old male mice fasted 16 h (n = 6). j Volcano plot of the differential lipids between the livers (n = 6 per group). k Pathway enrichment analysis using Ingenuity Pathway Analysis (IPA) of the lipidomic and RNA-seq data. l Enrichment level of the subcategories of liver steatosis shown in (k). Gray squares indicate the activate patterns of the subcategories are not available in reference. m Heatmap showing differential hepatic steatosis-related genes in Usp39-HKO mice compared to control mice (n = 4 per group). n IPA analysis of hepatic steatosis-related genes using RNA-seq data in control and Usp39-HKO mice. Correlation of differential genes with hepatic steatosis were shown with arrows (activation), and dashes (inhibition). Images are representative of at least three independent experiments. The p-value was obtained by IPA (k–l) and others performed unpaired two-sided Student’s t-test, and the results are presented as the mean ± S.D. NS, stands for non-significant. Source data are provided as a Source data file.