Fig. 5.

The secretory transport of 4F is modulated by TICE. A: Levels of neutral sterols in the feces from Tg112 and littermate control mice fed a chow diet (n = 8/group) were compared by GC/MS. B: WD has been shown to upregulate TICE in Tg112 mice. Male and female Tg112 mice were fed chow or WD for 6 weeks (n = 4 mice/gender/group), injected with 675 μg per mouse of ¹⁴C-l-4F (∼25 mg/kg) via the tail veins, and the radioactivity in the lumen washes was determined after 1 h. WD significantly upregulated 4F transport in both male (* P = 0.007) and female mice (** P = 0.005). While male and female mice exhibited no significant difference on chow (P = 0.2), male mice had significantly higher transport of 4F into the SI lumen than female mice when both were fed a WD (*** P = 0.008). C: Total neutral sterols were determined by GC/MS in the feces of the individual mice in B. WD significantly increased neutral sterols in the feces of both male (* P = 0.001) and female mice (** P = 0.02). While male and female mice exhibited no significant difference on chow, male mice had significantly more neutral sterols in their feces compared with female mice when both were fed a WD (*** P = 0.01). D: C57BL/6J mice were injected with 800 μg (∼25–30 mg/kg)/300 μl saline of d-4F via their tail veins (n = 7). After 30 min, the mice were euthanized and duodenal tissue explants were mounted in Ussing chambers. Each mouse contributed paired explants, whose serosal side media both did or did not contain LDL + HDL. Levels of both d-4F and cholesterol in mucosal media were determined by LC/MS/MS and GC/MS, respectively. The presence of serosal side lipoproteins significantly enhanced the transport of both d-4F and cholesterol into the mucosal media (*, ** P < 0.05). Error is reported as SEM.