The long-term goal is to understand the mechanisms of intestinal nutrient sensing and signal relays to insulin sensitive tissues (adipose, skeletal muscle, liver) in humans. The investigators hypothesize that human tissue biopsies (from obese surgery and non-surgery subjects as well as lean controls) can be used to understand the molecular mechanisms underlying intestinal nutrient sensing and signal relay in humans. The investigator will obtain tissue specimens from patients during scheduled upper endoscopies, colonoscopies and scheduled metabolic and bariatric surgeries or liver transplantation. A blood sample (4mL) will be obtained concurrent with these procedures. From metabolic and bariatric surgery subjects blood and tissues (liver, adipose, small intestine, omentum, skeletal muscle) can be collected at the time of surgery. From liver transplantation patients, excised liver tissue will be collected. Stool can be obtained preoperatively and at various time points after surgery. Some bariatric surgery subjects will participate in a mixed-meal tolerance test at their pre-operative visit and several post-operative visits to compare the whole-body metabolic alterations following bariatric procedures.
Upper endoscopy (subset) * Intestinal biopsies will be obtained during scheduled upper endoscopy from the mid-duodenum and/or proximal jejunum. In the case that a patient requires an upper endoscopy after metabolic and bariatric surgery, biopsies will be obtained from the mid-jejunum. * Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure. Colonoscopy (subset) * Biopsies of the colon will be obtained during scheduled colonoscopy. * Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure. Metabolic and bariatric surgery (subset) * During the metabolic and bariatric surgical procedures, biopsy of the jejunum, liver and omentum (visceral adipose) may be obtained. Biopsies of skeletal muscle and subcutaneous adipose will be taken at the sites of trocar placement for laparotomy. * Blood will be collected from an IV placed in the arm used for administering anesthesia required for the indicated procedure. * Feces will be self-collected by the patient using a provided culture swab specimen container or FOB card. Liver transplantation (subset) • Tissue will be collected from excised disease liver
Study Type
OBSERVATIONAL
Enrollment
500
Tissue samples will be collected from the jejunum, duodenum, and colon during the subject's standard of care procedure.
Biopsy of the liver is standard of care for diagnosing NAFLD. Biopsy of omentum, skeletal muscle and subcutaneous adipose (the latter two tissues taken at the site of trocar placement) will be collected intraoperatively at the time of Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG).
The mixed meal tolerance test (MMTT) shows how much insulin your body is making after drinking a liquid meal beverage that contains fats, protein and carbohydrates (sugar). Glucose, C-peptide, free fatty acids, triglycerides, incretins, pancreatic polypertide, bile aceis, and fatty acid amides can also be measured. A total of 9 tablespoons of blood is taken over a 255 minute period.
Tissue will be collected from the excised liver for research after the diseased liver has been removed as part of the standard of care procedure.
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Ability to establish organoid cultures
Measure percent success rate of making organoid cultures from tissue biopsies
Time frame: 12 months
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