Effect of Bariatric Surgery on Bile Acid Homeostasis

Morbid Obesity

The purpose of this study is to evaluate the effect of bariatric surgery in bile acid homeostasis and its interrelationship with the metabolic changes induced by the surgery. This study contemplates the following hypothesis: * Bariatric Surgery induce a new study state in bile acid homeostasis with higher bile acid synthesis in association with increased bile acid content. * The major effects of bariatric surgery on bile acid synthesis and is observed one month after surgery with a progressively decline during the first year of follow-up. * Gastric bypass increases serum bile acid content, postprandial plasma bile acid response and fecal bile acid excretion. * Serum bile acids changes induced by gastric bypass are positively correlated with changes in gastric inhibitory polypeptide (GIP) levels and postprandial concentration of insulin and glucagon like peptide-1 (GLP-1) and inversely correlated with thyrotropic hormone (TSH) and postprandial concentration of glucose. * Changes in postprandial plasma bile acid response induced by gastric bypass positively correlates with changes in postprandial concentration of insulin, GLP-1 and peptide YY (PYY) and inversely correlates postprandial response of ghrelin and glucose.

The proposed study will be conducted in adult subjects that will undergo to gastric bypass,sleeve gastrectomy or endoscopic duodenal-jejunal bypass. as treatment for their obesity. As a first approach (Protocol A) in each of these groups the investigators will determine 7α-hydroxy-4-cholestene -3-one (C4) levels, a marker of bile acid synthesis, and fibroblast growth factor 19 (FGF19), inhibitor of the expression of Cholesterol 7- hydroxylase (CYP7A1), prior to surgery and then at months 1, 3, 6 and 12 of postoperative follow-up. The same measurements will be performed to a group of patients under medical treatment when they achieve 10-kg diet-induced weight loss, which is equivalent to one-month of surgically induced weight loss. Preliminary studies suggest that gastric bypass induces a greater weight loss and improvement of associated disease compared with sleeve gastrectomy and endoscopic duodenal-jejunal bypass. Therefore, we expect a deeper change in bile acid homeostasis after gastric bypass, than after the other procedures. For this reason, in patients with gastric bypass the investigators will determine fecal excretion, synthesis, bile acid pool composition, and postprandial plasma response (Protocol B). These variables will be measured prior to surgery and one month after the procedure and also to the group of patients under medical treatment after a 10-kg diet-induced weight loss. The expression of diverse enzymes, nuclear receptors, transcription factors, transporters as well as cell surface receptors will be quantified at messenger ribonucleic acid (mRNA) and protein level in liver biopsy samples obtained from patients at the time of gastric bypass or sleeve gastrectomy (Protocol C). Those parameters will be reevaluated in liver samples obtained from the same subjects within the first 12 months of the postoperative follow-up.

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