Intestinal neutral ceramidase deficiency attenuates diet-induced MASH. (IMAGE)
Caption
WT mice or Asah2ΔIEC mice were fed the WD for 12 months. (A) Ratio for liver to body weight. (B–C) Representative liver images of Masson’s trichrome staining with quantification of aniline blue-positive area (B) and H&E staining with quantification of per cent lipid droplet area (C). (D) Level of hepatic TG. (E) α-SMA immunofluorescence (green) and DAPI counterstain (blue) and quantification. (F) Level of serum hydroxyproline. (G) Analysis of serum levels of ALT, AST, cholesterol, TG, glucose and VLDL by Piccolo Kits. (H) mRNA levels of the indicated genes related to fibrosis in the liver. (I) Flow cytometry analysis of CD11b+F4/80+MHCII−CD206+ macrophages in the liver. (J–K) Flow cytometry analysis of the percentage (J) and number (K) of TIM4−CLEC2−CD11b+F4/80+ macrophages (R1), TIM4+CLEC2− CD11b+F4/80+ cells KCs (R2) and TIM4−CLEC2+CD11b+F4/80+ KC-like cells (R3) in the liver. Φ: Macrophages. Here and thereafter, error bars represent mean±SEM. Statistical comparisons were performed using two-tailed unpaired Student’s t-test (A–F, I, J) for two groups; one-way ANOVA with Tukey’s multiple comparisons test for more than two groups; and two-way ANOVA with Sidak’s multiple comparisons test (G–H, K) with two factors. n=5. Independent biological samples. *p<0.05, ** p<0.01. Each dot represents one mouse (A, D, F–J). Scale bars: 100 µm (B), 50 µm (C, E). ALT, alanine aminotransferase; ANOVA, analysis of variance; AST, aspartate aminotransferase; DAPI, 4′,6-diamidino-2-phenylindole; FITC, fluorescein isothiocyanate; IEC, intestinal epithelial cell; MASH, metabolic dysfunction-associated steatohepatitis; MHC, major histocompatibility complex; mRNA, messenger RNA; ns, not significant; TG, triglyceride; VLDL, very low-density lipoprotein; WD, Western diet; WT, wild-type.
Credit
By Ting Wang, Liang Chen, Chao Lei, et al.
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted.
License
CC BY-NC