Physiologic and Functional Adaptations of Insulin Sensitive Tissues

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

Eligibility Criteria:
Inclusion Criteria:

- Scheduled for upper endoscopy, colonoscopy or metabolic and bariatric surgery, or liver transplantation at Vanderbilt University Medical Center.

Additional inclusion criteria for individuals scheduled for metabolic and bariatric surgery: Obese, ≥ 40 kg/m2 or ≥ 35 kg/m2 + one comorbidity (type 2 diabetes \[fasting blood glucose ≥ 120 mg/dL; HbA1C ≥ 6.5%\]; fatty liver disease, hypertension, cardiovascular disease, hyperlipidemia)

Additional inclusion criteria for individuals scheduled for liver transplantation: diagnosis of nonalcoholic liver disease or nonalcoholic steatohepatitis

Exclusion Criteria:

* Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease) and celiac sprue.
* Smoking \>7 cigarettes per day
* Malabsorptive syndromes
* Pregnant or breastfeeding

Additional exclusion criteria for patients undergoing endoscopy/colonoscopy:

* Recent history of malignancy (\<5 years ago)
* Previous lap band surgery
* Established renal disease

Additional exclusion criteria for patients undergoing bariatric surgery:

* Previous lap band, sleeve gastrectomy, or gastric bypass surgery
* Recent history of malignancy (\< 5 years ago)
* Established organ dysfunction

Additional exclusion criteria for patients undergoing liver transplantation:

* Previous lap band, sleeve gastrectomy, or gastric bypass surgery
* Alpha 1 anti-trypsin disease, Wilson's disease, viral hepatitis, alcoholic liver disease