Characterization of Bile Acid Pathway in Obesity

This is a single center study involving diet intervention, including healthy obese and healthy normal weight participants. Participants will maintain their normal diet for 1 week, eat a high fat and high calorie diet for 1 week, return to their normal diet for 1 week, and eat a low fat and low calorie diet for 1 week, to study the effect of diet on the bile acid pathway in normal weight and obesity. During their first normal diet week, the high calorie week, and the low calorie week, blood samples will be collected at defined times to measure cholesterol, glycemia, Fibroblast Growth Factor 19 (FGF-19), Bile Acid (BA), C4, and incretins (GLP-1 (glucagon-like peptide-1), peptide tyrosine tyrosine (PYY 3-36)) fasting levels and responses to the meal. Stool samples will be collected for 48 hour BA excretion.

Normal Weight Inclusion Criteria:

• Women of childbearing potential will have negative pregnancy tests within 48 hours of enrollment
• BMI: 18.5-25 kg/m2

Obese Inclusion Criteria:

• Women of childbearing potential will have negative pregnancy tests within 48 hours of enrollment
• BMI: ≥ 30 kg/m2

Exclusion criteria

for both Normal Weight and Obese Participants:

• History of abdominal surgery including cholecystectomy and other than appendectomy, Caesarian section or tubal ligation.
• Positive history of chronic gastrointestinal diseases, or systemic disease that could affect gastrointestinal motility, or use of medications that may alter gastrointestinal motility, appetite or absorption, e.g., orlistat, phentermine.
• Significant untreated psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Inventory (HAD), a self-administered alcoholism screening test (AUDIT-C) and the Questionnaire on Eating and Weight Patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a HAD score >11 or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up. The AUDIT-C is a 3-item alcohol screening questionnaire that reliably identifies participants who are hazardous alcohol drinkers or have active alcohol use disorders. In men, a score of 4 or more is above the recommended limits will be reviewed by study personnel. In women, a score of 3 or more is above the recommended limits will be reviewed by study personnel. However when the points are above recommended limits, the provider will review the patient's alcohol intake over the past few months to confirm accuracy and determine study eligibility..
• Intake of medication, whether prescribed or over the counter (except multivitamins), within 7 days of the study. Exceptions are birth control pill, estrogen replacement therapy, and thyroxin replacement therapy.