fMRI and Appetite-Related Hormones Pre and Post Obesity Surgery

The investigators are looking at the differences in appetite and obesity between weight loss participants and patients undergoing bariatric surgery. Obese persons between the ages of 18 & 65 are eligible to participate in this study, whether or not they intend to undergo bariatric 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.

30 subjects who plan to undergo Roux-en-Y Gastric Bypass bariatric surgery. Liquid meal responses and Behavioral fMRI responses to food-cues will be assessed before surgery (T1), 3 months (T2) and 18 months (T3) after surgery.

30 subjects who plan to undergo Gastric Banding bariatric surgery. Liquid meal responses and Behavioral fMRI responses to food-cues will be assessed before surgery (T1), 3 months (T2) and 18 months (T3) after surgery.

30 subjects who plan to begin a formula diet to lose weight. Liquid meal responses and Behavioral fMRI responses to food-cues will be assessed before subjects undertake a 12-week weight loss intervention (T1), at the end of the weight loss intervention (T2) and 18 months after they completed the weight loss intervention(T3).

30 subjects who do not undergo any treatment for weight loss. Liquid meal responses and Behavioral fMRI responses to food-cues will be assessed at baseline (T1) and at 3 months (T2) and 18 months (T3) later.

30 subjects who plan to undergo Sleeve Gastrectomy bariatric surgery. Liquid meal responses and Behavioral fMRI responses to food-cues will be assessed before surgery (T1), 3 months (T2) and 18 months (T3) after surgery.

Subject ingests a meal-replacement shake and gut peptide levels are measured before and after intake.

Measures of brain brain activation in areas associated with food reward and motor planning, including the orbitofrontal cortex (OFC). Over the course of 40-min fMRI scans, we will compare change in activation from 3 mo pre-surgery to 3 and 18 mo post-surgery, and predict a post-surgical decrease in activation in such regions.

Height and weight will be assessed using a stadiometer and digital scale. Sagittal diameter and waist and hip circumferences, as well as maximum supine width, will be measured. Waist circumference will be measured. Air displacement (Bioelectrical impedance analyses) will also be performed to obtain lean and fat mass. Weights, BMI, and body composition will confirm that the four obese groups are similar at baseline and provide estimates of changes in body fat following treatment.

We will administer relevant psychological instruments to assess Mood: The Inventory of Depressive Symptomatology-Self Report (IDS-SR)will be assessed at 3mo pre-surgery, 3mo, 6mo and 18mo post surgery.

We will measure changes in appetite-related gut peptide levels before and following a fixed meal prior to the fMRI. This will be assessed via blood plasma samples taken on 3 occasions: 3 mo pre-surgery, 3 mo post-surgery, and 18 mo post-surgery. At each session, there will be multiple time points: -15, 0, 15, 30, 60, and 90 minutes before/after ingestion of a meal replacement shake.

We will administer relevant psychological instruments to assess Eating Behavior:including Eating Disorder Examination (EDE) to diagnose BED; Binge Eating Scale (BES), correlated with BED status; eating-related behavior (DEBQ - Restraint, Emotional, and Externality subscales); and dietary intake (24-Hour Food Recall).

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