Figure 4

Sort1 deficiency reduced Npc1l1 and plasma cholesterol absorption in murine jejunum and human Caco-2 cells. (a) 15-week NC or HF/HC-fed female mice plasma total cholesterol (TC) and triglyceride (TG) levels (n = 8–10 mice/group), and (b) fecal TC and TG levels in female Ldlr−/−Sort1+/+ and Ldlr−/−Sort1−/− mice fed a HF/HC diet for 15 weeks (n = 5–6 mice/group). (c) Npc1l1, Npc1l1 regulators, and cholesterol efflux genes mRNA levels in female mouse jejunum (n = 6 mice/group). (d) ex vivo fluorescent cholesterol absorption analysis in mouse jejunum treated with or without ezetimibe; (n = 6–7 mice/group). (e) mRNA levels of NPC1L1 and NPC1L1 regulators (n = 6), and (f) cholesterol absorption in Caco-2 cells with SORT1 RNA interference (siSORT1) or scrambled control (Scr), with or without ezetimibe treatment; (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 versus Ldlr−/−Sort1+/+ or Scr; analyzed by t-test, except the TC and TG data in panel 4a that were analyzed by ANOVA with Tukey’s multiple comparisons test, and cholesterol absorption data in panels 4d and 4 f that were analyzed by ANOVA with Dunnett’s multiple comparisons test; values are presented as mean ± SEM.