Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat
Résumé
MINI-ABSTRACT
We 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 main
metabolic benefits of GBP: 1) improved glucose control, 2) decreased food intake because of
disinterest in high calorie food.
STRUCTURED ABSTRACT
Objective: To evaluate the role of bile routing modification on the beneficial effects of gastric bypass
surgery on glucose and energy metabolism.
Summary background data: Gastric bypass surgery (GBP) promotes early improvements in glucose
and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in
hepatic 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 midjejunum
or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body
weight, food intake, glucose tolerance, insulin sensitivity and food preference were analyzed. The
expression 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 marked
improvement in glucose control. Bile bioavailability modification is causal since a bile acid
sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with
the 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 acquired
disinterest in fatty food.
Conclusion: This study shows that bile routing modification is a key mechanistic feature in the
beneficial outcomes of GBP.
Domaines
Neurosciences [q-bio.NC]
Origine : Fichiers produits par l'(les) auteur(s)
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