The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control

Author:

Pournaras Dimitri J.12,Glicksman Clare3,Vincent Royce P.13,Kuganolipava Shophia4,Alaghband-Zadeh Jamie3,Mahon David2,Bekker Jan H.R.5,Ghatei Mohammad A.1,Bloom Stephen R.1,Walters Julian R.F.4,Welbourn Richard2,le Roux Carel W.16

Affiliation:

1. Department of Investigative Medicine (D.J.P., R.P.V., M.A.G., S.R.B., C.W.l.R.), Imperial Weight Centre, Imperial College London, London W6 8RF, United Kingdom

2. Department of Bariatric Surgery (D.J.P., D.M., R.W.), Musgrove Park Hospital, Taunton TA1 5DA, United Kingdom

3. Department of Clinical Biochemistry (C.G., R.P.V., J.A.-Z.), King's College Hospital, London SE5 9RS, United Kingdom

4. Department of Gastroenterology (S.K., J.R.F.W.), Imperial College London, London HA7 4FG, United Kingdom

5. Department of Surgery (J.H.R.B.), University of Pretoria, Pretoria 5100, South Africa

6. Experimental Pathology (C.W.l.R.), Conway Institute, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland

Abstract

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.

Publisher

The Endocrine Society

Subject

Endocrinology

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