Gastric bypass surgery (GBP) promotes early benefits in energy homeostasis in obese diabetic patients, including decreased hunger and improved glucose control. A suggested mechanism associates a decrease in hepatic glucose production (HGP) with an enhanced intestinal gluconeogenesis (IGN), the latter promoting metabolic benefits in energy homeostasis. In addition, bile acids (BA) have emerged as key metabolic regulators, which might account for several anti-diabetic effects. Moreover, plasma bile acids are elevated after GBP and are known to inhibit gluconeogenesis. Bile diversions mimicking GBP in lean rats (re-insertion of bile in the mid-jejunum or the mid-ileum) 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 obese rats fed a high fat-high sucrose diet, bile diversions improve glucose control and dramatically decrease food intake. This is due to an acquired disinterest for fatty food, leading the animals to prefer starch-enriched diet. These data suggest a key role of bile and of gluconeogenesis in the favorable outcomes of metabolic surgery.
20 - 23 May 2017
European Society of Endocrinology