Changes in Bile Acid Profile After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Metabolic Profile and Fatty Liver Disease.

BACKGROUND: Bile acids (BA) modulate lipid and glucose metabolism in a feedback loop through production of fibroblast growth factor (FGF) 19 in the terminal ileum. Changes in BA after bariatric surgery may lead to improvements in the metabolic syndrome, including fatty liver disease. This study investigated the relationship between BA and metabolic and inflammatory profiles after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients undergoing LSG had fasting blood samples taken pre-operatively and 6 months post-surgery. Liver injury was measured using cytokeratin (CK) 18 fragments. BA were measured using liquid chromatography tandem-mass spectrometry. FGF-19 was measured using enzyme-linked immunosorbent assay. RESULTS: The study included 18 patients (12 females), with mean age 46.3 years (SEM ± 2.9) and BMI 60.1 kg/m(2) (±2.6). After 6 months, patients lost 39.8 kg (±3.1; p < 0.001). Fourteen patients (78 %) had steatosis. FGF-19 increased from median 128.1 (IQR 89.4-210.1) to 177.1 (121.8-288.9, p = 0.045) at 6 months. Although total BA did not change, primary glycine- and taurine-conjugated BA, cholic acid decreased, and secondary BA, glycine-conjugated urodeoxycholic acid increased over the study period. These changes are associated with reduction in insulin resistance, pro-inflammatory cytokines and CK-18 levels. CONCLUSIONS: The profile of individual BA is altered after LSG. These changes occur in the presence of reductions in inflammatory cytokines and markers of liver injury. This study supports evidence from recent animal models that LSG may have an effect on fatty liver through changes in BA metabolism.

The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control.

Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.