title: Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat.
abstract: OBJECTIVE
  To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism.
  
  
  BACKGROUND
  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 to an enhanced intestinal gluconeogenesis. 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 because 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 hepatic glucose production, whereas intestinal gluconeogenesis 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 because of an acquired disinterest in fatty food.
  
  
  CONCLUSIONS
  This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Lyon, France, Université de Lyon, Lyon, France, Université Lyon 1, Villeurbanne, France.
authors.forename: Daisy
authors.initials: D
authors.lastname: Goncalves
authors.forename: Aude
authors.initials: A
authors.lastname: Barataud
authors.forename: Filipe
authors.initials: F
authors.lastname: De Vadder
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vinera
authors.forename: Carine
authors.initials: C
authors.lastname: Zitoun
authors.forename: Adeline
authors.initials: A
authors.lastname: Duchampt
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
mesh_terms: D000818:Animals; D001646:Bile / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D004734:Energy Metabolism; D005518:Food Preferences / Q000502:physiology; D015390:Gastric Bypass; D005786:Gene Expression Regulation; D005943:Gluconeogenesis / Q000235:genetics; D006706:Homeostasis; D007082:Ileum / Q000601:surgery; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000601:surgery; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D001786:Blood Glucose