Study of Effects From Gastric Bypass Weight Loss on Brain Tissue

This study will evaluate how large, intentional weight reduction affects the human brain and possible ways to reverse the changes associated with excess body weight. Subtle changes in some brain regions occur in people who are overweight. Such changes may involve the regulation of eating behavior, though it is not clear whether the changes were present before weight gain or are a consequence. Magnetic resonance imaging (MRI) will be used to study local structures of the brain. Patients ages 18 to 45 who are undergoing gastric bypass surgery and who are not pregnant or breastfeeding may be eligible for this study. A study group of lean participants will serve as controls. Patients will visit the Phoenix Indian Medical Center for about 3 days at a time for tests. They will have a medical examination, electrocardiogram, and tests of blood and urine. Questionnaires they will complete involve patients' moods and possible influence on eating behaviors, as well as food preferences. A taste test, smell test, and assessment of decision-making processes will be conducted. An oral glucose tolerance test involves a needle placed intravenously (IV) in the arm, for drawing blood after patients drink a sugar solution. The test takes about 3-1/2 hours, with six blood samples taken (about 2 tablespoons total). A meal test also includes use of an IV line. After patients consume a liquid meal, blood will be collected to analyze levels of blood sugar and hormones. For the DEXA scan, which measures body composition, patients will lie still while low-dose X-rays are used for 5 to 10 minutes. Urine will be collected for 1 whole day, to measure cortisol, a hormone. The MRI scan uses a strong magnetic field to obtain images of body organs and tissues. Patients having any metal in the body that may interfere with the scanning machine should not have this test. For the MRI procedure, patients will lie on a table that slides into the enclosed tunnel of the scanner and be asked to lie still. Patients will be able to communicate with the MRI staff at all times during the scan, and they may ask to be removed from the machine at any time.

BACKGROUND: We have identified subtle changes in some brain regions of obese subjects by using a new computerized technique (voxel-based morphometry, VBM) which allows for studying the local structure of the brain by taking very detailed pictures of the brain through magnetic resonance imaging (MRI) and then processing these images with sophisticated statistical software. Some of these regions may interfere with an obese person's ability to predict future consequences of his or her eating behaviors. These changes may explain why people have difficulty losing weight. However, it is not clear whether these changes in the brain are present before or are a consequence of weight gain. OBJECTIVES: The main aim of this study will be to evaluate the effects of a large and intentional weight reduction on the brains of obese individuals for assessing the possible reversal of the changes associated with excess body weight. Additional objectives will be a) to determine the possible behavioral correlates of the changes in brain tissue composition associated with a large and intentional weight reduction and b) to confirm the results of our previous exploratory analysis showing that human obesity is associated with changes in brain structure in areas related to the regulation of eating behavior. DESIGN: This is a longitudinal protocol mainly focused on obese patients undergoing roux-en-Y gastric bypass (RYGBP), which represents the most effective approach currently available to achieving substantial weight loss, thus maximizing our chances of detecting significant changes in brain tissue composition. Therefore, we propose to study brain morphology and the metabolic and behavioral characteristics of 40 obese patients undergoing RYGBP prior to and 3, 6, 12, 24, and 48 months after the surgery. Forty lean subjects (at 0, 12, 24, and 48 months) will also be studied for comparison. OUTCOME MEASURES: The volumes of the different components of the brain by VBM of MRI pictures; metabolic parameters relevant to the relationship between obesity and the brain by measuring fasting concentrations and postprandial responses of some metabolites; the ability to regulate reward and behavior by specific tasks and questionnaires; the ability to detect and discriminate smells by olfaction tests.