Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model

Abstract

The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the one anastomosis gastric bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces similar beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the length of biliary and common limbs in the weight loss and metabolic effects that occur upon OAGB. OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss.NEW & NOTEWORTHY Common limb mediates postprandial glucose metabolism change after gastric bypass whereas biliary limb contributes to weight loss.

Keywords: bariatric; bariatric surgery; bile acids; biliary limb; bypass; common limb; one anastomosis gastric bypass.

Graphical abstract

Figure 1.

Bypass procedures. A and B: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB). Red arrow: alimentary limb, green arrow: biliary limb, and blue arrow: common limb. Surgical procedures. C–F: sham procedure (Sham), and OAGB procedure (OAGB), sham with resection of the common limb procedure (Sham-res), and OAGB with resection of the biliary limb procedure (OAGB-res). Blue arrows represent transit in the common limb (CL) and green arrows represent transit in the biliary limb (BL).

Figure 2.

Weight loss and metabolic response to the mixed-meal test. A: weight loss at 10 and 20 days after surgery; B: blood glucose excursion (incremental blood glucose) during the mixed-meal test (MMT); C: postprandial glucose response (incremental AUC for blood glucose); D: d-xylose plasmatic profile during the MMT; E: incremental area under the curve for d-xylose; F: incremental GLP-1 excursion during the MMT; G: incremental area under the curve for GLP-1; H: incremental insulin excursion during the MMT; I: incremental area under the curve for insulin. Blue dot: Sham group, green dot: OAGB group, blue bar: Sham group, and green bar: OAGB group. Statistical analysis: two-way ANOVA (A), one-way ANOVA (C, E, G, and I). *P < 0.05; ***P < 0.001. AUC, area under the curve; GLP-1, glucagon-like peptide 1; OAGB, one anastomosis gastric bypass.

Figure 3.

Plasma BA signatures. A: total BA concentration (nM); B: BA species concentration (nM). Blue bar: Sham group and green bar: OAGB group. CA, cholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; LCA, lithocholic acid; UDCA, ursodeoxycholic acid; HCA, hyocholic acid; HDCA, hyodeoxycholic acid. Statistical analysis: (A) t test and (B) Mann–Whitney test. *P < 0.05; **P < 0.01. BA, bile acid; OAGB, one anastomosis gastric bypass.

Figure 4.

Signatures of the intestinal BAs. Localization of sampling along the GI for BA signature determination in Sham group (A) and OAGB group (B). Intestinal BA signature in gall bladder (C), proximal biliary limb (D), distal biliary limb (E), proximal common limb (F), distal common limb (G); cecal content (H), and feces (I). J: intestinal free/conjugated BA ratio; K: intestinal primary/secondary BA ratio (C–K). Blue bar: sham group and green bar: OAGB group. Statistical analysis: linear trend and two-way ANOVA (A), two-way ANOVA (B), and one-way ANOVA (E–K). ***P < 0.001. BA, bile acid; GI, gastrointestinal; OAGB, one anastomosis gastric bypass.

Figure 5.

Intestinal bile transporters and markers of hepatic BA synthesis. A–E: mRNA relative levels of apical sodium bile acid transporter (ASBT) (A), ileal bile acid binding protein (IBABP) (B), organic solute transporter α (OST α) (C), organic solute transporter β (OSTβ) (D), hepatic enzyme and BA transporters (E), and C4 plasma concentration (nM) (F). Statistical analysis: (A–D) Kruskal–Wallis test; (E) Mann–Whitney test; and (F) one-way ANOVA. *P < 0.05. BA, bile acid.

Figure 6.

Metabolic phenotype after limb shortening. A: weight loss at 10 and 20 days after surgery; B: blood glucose excursion (incremental blood glucose) during the mixed-meal test (MMT); C: postprandial glucose response (incremental AUC for blood glucose); D: d-xylose plasmatic profile during the MMT; E: incremental area under the curve for d-xylose; F: incremental GLP-1 excursion during the MMT; G: incremental area under the curve for GLP-1; H: incremental insulin excursion during the MMT; and I: incremental area under the curve for insulin. Green dot: OAGB group, white dot with green lining: OAGB-res group, and white dot with blue lining: Sham-res group. Green bar: OAGB group, white bar with green lining: OAGB-res group, and white bar with blue lining: Sham-res group. Statistical analysis: (A) two-way ANOVA and (C, E, G, and I) one-way ANOVA. *P < 0.05 vs. Sham; ***P < 0.001 vs. Sham; #P < 0.05 vs. OAGB-res; @@P < 0.01 vs. Sham-res. AUC, area under the curve; GLP-1, glucagon-like peptide 1; OAGB, one anastomosis gastric bypass.