fMRI and Appetite-Related Hormones Pre and Post Obesity Surgery

Currently, the only effective long term treatment for severe obesity is bariatric surgery.2 Nearly 200,000 procedures are performed each year, with this number increasing rapidly.3 However, the mechanisms of reduced food intake and weight loss after obesity surgery, particularly Rouen-Y gastric bypass (RYGB), are not well understood. This study utilizes functional magnetic resonance imaging (fMRI) and measures of appetite-related gut peptide levels pre and post bariatric surgery to investigate the neurological and hormonal mechanisms involved in initiation and termination of meals.

The general objective is to better understand the physiological changes resulting in weight loss from obesity surgery, particularly Roux-en-Y gastric bypass (RYGB). The main hypothesis is that the differential mechanisms of action in RYGB will alter the signals involved in the initiation and termination of meals, reflected by changes in both peptide hormone levels and regional brain activity in response to foods. The investigators anticipate that the trigger for meal initiation by potent food stimuli will be diminished following RYGB, as indicated by reduced brain activation in areas associated with food reward and motor planning, including the orbitofrontal cortex (OFC). RYGB will be compared to: a. Gastric Banding (GB), representing the restrictive component of surgery, which itself enhances fullness, but in the absence of any rerouting of the gut, should result in fewer changes in gut peptide levels and brain activation; b. Weight Loss (WL) on a formula diet over 3 mo, which represents the weight loss component of surgery; and c. No Treatment (NT), a general control, with no gastric restriction or weight loss. These group comparisons will help parse the contributions of RYGB surgery to weight loss.

The plan is to study clinically severe obese subjects (S's) pre surgery, and at 3 and 18 mo post surgery. The investigators will examine: 1) fMRI brain activation in response to food stimuli and 2) appetite-related gut peptide levels before and following a fixed meal prior to the fMRI. The findings should reveal potential mechanisms associated with the changes in appetite, eating behaviors, and body weight, both during the rapid weight loss phase at 3 mo post surgery as well as when weight typically stabilizes at a nadir at 18 mo post surgery. The investigators plan to enroll 160 patients: 40 with RYGB, 40 GB, 40 WL, and 40 NT (4-arm study). S's will be within the BMI range of 40-50 and matched across groups for BMI, gender (3:1, f:m), and BED status.

Inclusion criteria

• BMI range 35-50 kg/m^2

Exclusion criteria

• diabetes,
• smoking,
• pregnancy