Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans

Role of the Foregut in Nutrient Metabolism in Lean and Obese Humans

The overall hypothesis of this proposal is that nutrient sensing in the foregut regulates metabolic hormone secretion and nutrient metabolism via enteric neural signals, and these mechanisms might be defective in obesity.

The study proposes two specific aims Aim 1 will determine if blocking enteric neuronal signaling will alter: a) circulating levels of nutrient substrates and secretion of hormones that regulate nutrient metabolism; and b) glucose and fatty acid absorption, production, and utilization.

Obese (BMI = 30-50 kg/m2) subjects will be studied. The topical anesthetic benzocaine will be infused into the duodenum prior to infusion of glucose and oleic acid into the duodenum. Duodenal infusions with a naso-intestinal feeding tube will circumvent the confounding effects of gastric emptying on the metabolic responses to a meal. Substrates (glucose, free fatty acids), and lipoproteins) and hormones will be measured by standard biochemical and immunological methods. Aim 2 will determine if enteric neural signals regulate appetite. The studies will be carried out in both lean and obese humans and the procedure will be performed as described above. In addition, the subjects will be asked to use a visual analog scale to estimate their level of appetite before, during and after enteral infusions.

Inclusion Criteria:

• BMI 19 - 25 kg/m2 or 30 - 50 kg/m2
• Age 20 - 50 years

Exclusion Criteria:

• Contraindication to a nasoduodenal feeding tube (e.g., deviated nasal septum, prior upper gastrointestinal bleed, or history of easy bleeding)
• Prior gastric or intestinal surgery or pancreas resection
• Females with a positive pregnancy test
• Known history of intestinal diseases including, but not limited to, inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), celiac sprue
• Type 1 or type 2 diabetes
• Recent presence of or treatment for gastroenteritis (diarrhea and/or vomiting), constipation, or upper respiratory infection
• Anemia
• Abnormal electrocardiogram
• Prior adverse reaction to anesthesia
• Tobacco use