Effect of Bariatric Surgery on Bile Acid Homeostasis
Condition: Morbid Obesity
MeSH terms: Obesity, Morbid
Study type: Observational [Patient Registry]

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Obese patients that have undergone bariatric surgery or medical treatment to lose weight.
      
Biospecimen description: 
      -  Blood samples (serum and plasma).

        -  Stool samples.

        -  Liver samples.