Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway

Figure 1 Body weight and energy intake from baseline to week 12 after operations as well as oral glucose tolerance test and the corresponding areas under the curves at baseline, week 4 and week 12 after operations. A: Body weight; B: Energy intake; C: Area under the curve of oral glucose tolerance test; D: Oral glucose tolerance test at baseline; E: Oral glucose tolerance test at week 4; F: Oral glucose tolerance test at week 12. ^aP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass + chenodeoxycholic acid; ^bP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass. SHAM: Salicylhydroxamic acid; DJB: Duodenal-jejunal bypass; CDCA: Chenodeoxycholic acid.

Figure 2 Luminal total and individual bile acid concentrations and ceramide concentrations within the peripheral and portal circulations. A: Total amount of luminal bile acids; B: Luminal individual bile acid percentage in the proximal; C: Medium segment within the common limb; D: Distal segment within the common limb; E: Ratio of farnesoid X receptor agonist and antagnist within the common limb; F: Peripheral serum ceramides; G: Portal serum ceramides. ^aP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass + chenodeoxycholic acid; ^bP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass; ^cP < 0.05, duodenal-jejunal bypass vs duodenal-jejunal bypass + chenodeoxycholic acid. FXR: Farnesoid X receptor; SHAM: Salicylhydroxamic acid; DJB: Duodenal-jejunal bypass; CDCA: Chenodeoxycholic acid; αMCA: α-muricholic acid; UDCA: Ursodeoxycholic acid; LCA: Lithocholic acid; HDCA: Hyocholic acid; TLCA: Taurine-conjugated lithocholic acid.

Figure 3 Expression of ceramide synthesis-related enzyme sphingomyelin phosphodiesterase 3 and serine palmitoyltransferase long chain base subunit 2 at protein and mRNA levels. A: Expression of sphingomyelin phosphodiesterase 3 (Smpd3), serine palmitoyltransferase long chain base subunit 2 (Sptlc2) and GAPDH; B: Expression of Smpd3, Sptlc2 at protein; C: Expression of Smpd3, Sptlc2 mRNA levels. ^aP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass + chenodeoxycholic acid; ^bP < 0.05, salicylhydroxamic acid vs duodenal-jejunal bypass; ^cP < 0.05, duodenal-jejunal bypass vs duodenal-jejunal bypass + chenodeoxycholic acid. SHAM: Salicylhydroxamic acid; DJB: Duodenal-jejunal bypass; CDCA: Chenodeoxycholic acid; Smpd3: Sphingomyelin phosphodiesterase 3; Sptlc2: Serine palmitoyltransferase long chain base subunit 2.