Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans

• Published in: International Journal of Obesity 2016-08, Vol.40 (8), p.1260-1267
• Main Authors: Spinelli, V, Lalloyer, F, Baud, G, Osto, E, Kouach, M, Daoudi, M, Vallez, E, Raverdy, V, Goossens, J-F, Descat, A, Doytcheva, P, Hubert, T, Lutz, T A, Lestavel, S, Staels, B, Pattou, F, Tailleux, A
• Format: Article
• Language: English
• Subjects: 101/58; 631/443/319/1642/393; 631/45; 692/163; 692/700/565/545; Acids; Adult; Animal models; Animal research models; Animals; Bile; Bile acids; Bile Acids and Salts - blood; Blood Glucose - metabolism; Cardiology; Care and treatment; Chenodeoxycholic acid; Cholic acid; Comparative analysis; Comparative studies; Deoxycholic acid; Diabetes; Diabetes mellitus (non-insulin dependent); Disease Models, Animal; Epidemiology; Female; Gastric Bypass; Gastrointestinal surgery; Glucose; Health Promotion and Disease Prevention; Homeostasis; Humans; Internal Medicine; Lipids; Liquid chromatography; Liver; Male; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Microbiota; Middle Aged; Obesity; Obesity - blood; Obesity - physiopathology; Obesity - surgery; original-article; Peripheral blood; Physiological aspects; Physiological effects; Physiology; Plasma; Public Health; Rats; Signal Transduction; Signaling; Species; Swine; Swine, Miniature; Treatment Outcome; Weight control; Weight Loss
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2016.46

Background: Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential. Methods: Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP. Results: RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model. Conclusions: The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.