Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat

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Goncalves, Daisy | Barataud, Aude | de Vadder, Filipe | Vinera, Jennifer | Zitoun, Carine | Duchampt, Adeline | Mithieux, Gilles

Edité par CCSD ; Lippincott, Williams & Wilkins -

International audience. MINI-ABSTRACTWe performed bile diversions matching the modified biliary flow occurring after gastric bypass (GBP)in rats. Our results strongly suggest that the only modification of bile routing mimics the mainmetabolic benefits of GBP: 1) improved glucose control, 2) decreased food intake because ofdisinterest in high calorie food.STRUCTURED ABSTRACTObjective: To evaluate the role of bile routing modification on the beneficial effects of gastric bypasssurgery on glucose and energy metabolism.Summary background data: Gastric bypass surgery (GBP) promotes early improvements in glucoseand energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease inhepatic glucose production (HGP) to an enhanced intestinal gluconeogenesis (IGN). Moreover,plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis.Methods: In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the midjejunumor the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Bodyweight, food intake, glucose tolerance, insulin sensitivity and food preference were analyzed. Theexpression of gluconeogenesis genes was evaluated in both the liver and the intestine.Results: Bile diversions mimicking GBP promote an increase in plasma bile acids and a markedimprovement in glucose control. Bile bioavailability modification is causal since a bile acidsequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement withthe inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in HGP,whereas IGN is increased in the gut segments devoid of bile. In rats fed a high fat-high sucrose diet,bile diversions improve glucose control and dramatically decrease food intake due to an acquireddisinterest in fatty food.Conclusion: This study shows that bile routing modification is a key mechanistic feature in thebeneficial outcomes of GBP.

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