The Effect of Sleeve Gastrectomy on Post-prandial Serum Bile Acids
Condition: Obesity
MeSH terms: Obesity
Study type: Observational

Summary: 
      This is a prospective study of meal-induced bile acid physiology before and after sleeve
      gastrectomy (SG) surgery. Weight loss and metabolic improvement associated with weight loss
      surgery cannot be entirely attributed to restriction in stomach size and food intake. Bile
      acids (BAs), amphipathic steroids that have a role in lipid uptake and metabolism in the
      gastrointestinal tract, are involved in post-prandial glucose homeostasis and energy
      expenditure & are a potential intermediary in weight loss following bariatric surgery. It is
      unknown if SG increases post-prandial BAs in humans and if an increase in BA signaling
      impacts weight loss and co-morbidity resolution after surgery. The investigators hypothesis
      is that SG will increase the post-prandial serum and urine BAs and that the change in the BA
      profile is a mechanism for restriction-independent weight-loss following SG. SG patients will
      undergo a meal challenge pre-operatively, and at 1, 3, and 12 months post-operatively, with
      measurement of post-prandial serum and urine BAs and downstream hormones, glucagon-like
      peptide 1 (GLP-1) and fibroblast growth factor 19 (FGF19), and a scoring of satiety before
      and after the meal challenge using a Visual Analog Scale. Serum insulin, glucose, and C4
      levels will also be measured to assess metabolic changes associated with SG. Serum and urine
      BA levels will be compared to post-operative excess weight loss at 12 months. Before and
      after each meal challenge, patients will be asked to score satiety, and this will be
      correlated to weight loss, bile acids, GLP-1, and FGF19.
    

Detailed description: 
      SUMMARY Bariatric surgeries, such as sleeve gastrectomy (SG), have become an important
      therapeutic option for morbid obesity and the treatment of obesity-associated co-morbidities.

      There is evidence that the weight loss and metabolic improvements associated with SG cannot
      be entirely attributed to a restriction in stomach size nor nutrient malabsorption. Bile
      acids (BAs) are a novel potential intermediary in restriction-independent weight loss
      following SG. Bile acids are amphipathic steroids that have a role in lipid uptake and
      metabolism in the gastrointestinal tract as well as post-prandial glucose homeostasis and
      energy expenditure. BAs are the natural ligand for the nuclear farnesoid X receptor (FXR) and
      the BA activated, cell surface G-protein coupled receptor, TGR5. FXR activation inhibits
      lipogenesis, glycolysis, BA synthesis and stimulates FGF19 production, which functions in the
      regulation of BA synthesis. TGR5 activation increases energy expenditure and stimulates the
      enteroendocrine L cells to secrete the incretin hormone, glucagon-like peptide 1 (GLP-1).
      Both roux-en-y gastric bypass (RYGB) and SG, unlike gastric banding and dieting, have been
      shown to paradoxically increase energy expenditure and augment post-prandial GLP-1 secretion,
      suggesting a restriction-independent mechanism of weight-loss possibly mediated by changes in
      BA signaling [1-4]. Although suggested by animal models of SG, it is currently unknown if SG
      increases post-prandial BAs in humans and if an increase in BA signaling impacts weight loss
      and co-morbidity resolution following surgery. The identification of restriction-independent
      mechanisms of weight loss after SG may lead to the development of novel surgical or medical
      therapies that exploit these specific mechanisms to achieve significant and sustainable
      weight loss in morbidly obese patients. Further, understanding the mechanisms of weight loss
      after SG may lead to the identification of patients pre-operatively or early in the
      post-operative period who are at high risk for poor surgical weight loss outcomes. The
      proposed work is a prospective study of meal-induced BA physiology before and after SG.

      The investigators hypothesize that SG will increase the post-prandial serum and urine BAs and
      that the change in the post-operative bile acid profile is a mechanism for restriction
      independent weight-loss following sleeve gastrectomy.

      The investigators first specific aim is to determine the effect of SG on post-prandial total
      BAs and BA subtypes. The investigators working hypothesis is that SG will increase
      post-prandial total BAs as well as modulate specific BA subtypes. Eligible SG patients will
      undergo a meal challenge preoperatively, and at one, three, and 12 months post-operatively,
      with measurement of postprandial serum and urine bile acids by ultra-performance liquid
      chromatography and mass spectroscopy (UPLC/MS) as well as GLP-1 and FGF19 by ELISA. Serum
      insulin, glucose, and C4 levels will also be measured to assess metabolic changes associated
      with SG.

      The investigators second specific aim is to correlate the changes in post-prandial bile acids
      and bile acid subtypes after SG to post-operative excess weight loss and satiety. The
      investigators working hypothesis is that post-prandial BAs and BA subtypes will increase
      following SG, and the increase in bile acids will correspond to post-operative excess weight
      loss, GLP-1 production, and meal satiety. Post-prandial serum and urine BAs preoperatively
      and at 1, 3, and 12 months following SG will be compared to post-operative excess weight loss
      at 12 months. Before and after each meal challenge, patients will be asked to score satiety,
      and these scores will be correlated to excess weight loss, GLP-1 and total BA as well as BA
      subtypes.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Morbidly obese patients who are being treated in the Bariatric Clinic at the University of
        Nebraska Medical Center
      
Biospecimen description: 
      Serum Urine
    
Keywords: bile acids; sleeve gastrectomy; obesity; GLP-1; FGF-19