Physical Activity Following Surgery Induced Weight Loss

The primary objective of this study will be to determine the effects of physical activity in patients during substantial surgery-induced weight loss. We propose to employ a randomized controlled physical activity intervention trial in a group of patients undergoing bariatric surgery for weight loss. The study will involve two sites with an active bariatric surgery program, which have a strong track record of bariatric surgery research.

Recruitment goals are 160-200 gastric bypass patients who will undergo 6 months of moderate physical activity compared to an educational control group not engaged structured exercise. Subjects will be included if their BMI is less than 55 kg/m2 prior to surgery and they are located relatively close to centers for intervention sessions. At baseline (3 months following surgery) and 6 months later (9 months following surgery), subjects will have a CT scan, IV glucose tolerance test (IVGTT) and muscle biopsy (~8 hour visit). They will be scheduled for separate visits for a test of physical fitness (VO2max) and general body composition (DXA scan)(~2 hour visit), and a 15-min sub-maximal exercise session.

1. Physical activity group: Subjects will be progressed to 4-5 days per week, 30-45 min per session (120-180 min per week) of moderate intensity exercise.
2. Control (educational) group: Subjects will receive their usual care following surgery that includes information on physical activity. They will also be asked to participate in monthly health education sessions.

We will promote this study as one that will help determine whether physical activity may be beneficial in addition to their weight loss.

Aim 1: Insulin resistance and metabolic risk factors. Approach: To address Aim 1, we will determine 6-month changes in insulin sensitivity in subjects after 3-month initial weight loss from bariatric surgery. As outlined above, we will employ a randomized controlled physical activity intervention trial in which half of the subjects will be entered into a physical activity group, while the other half will participate in monthly health education sessions (control). By randomizing these groups three months after initial weight loss, both groups should begin the intervention with similar baseline characteristics (e.g. insulin sensitivity, body weight, physical fitness, etc.). We are not attempting to determine the effect of the weight loss per se on insulin sensitivity. However, we realize that the amount of weight loss could potentially have a major confounding influence on detecting changes in insulin sensitivity between the two groups. Thus, we will examine the degree of weight loss as a covariate in our analyses.

Aim 2: Intramyocellular lipids and body composition. Approach: We will examine pre to post intervention, changes in intramyocellular lipid determined with percutaneous biopsies, as well as abdominal and intermuscular adipose tissue determined by CT imaging.

Aim 3: Mitochondria content, function and fat oxidation. Approach: We will use three complimentary measures to quantify changes in oxidative metabolism before and after the randomized controlled trial described above. All three of these measures will make specific contributions to this specific aim. Rates of resting post-absorptive fat oxidation will be measured with indirect calorimetry. Since skeletal muscle accounts for the vast majority of energy production during physical activity, sub-maximal exercise is a good model to assess skeletal muscle fatty acid metabolism. We will employ whole body gas exchange indirect calorimetry during moderate exercise designed to elicit high rates of fatty acid oxidation. The non-invasive measures of systemic fat oxidation during both resting and exercise conditions procedures take very little time and present relatively little burden on the volunteers or technical staff, thus providing an efficient means to obtain significant information concerning the capacity for fat oxidation in vivo. Muscle biopsy samples will be obtained before and after the trial to measure changes in the oxidative capacity (electron transport chain activity, in vitro fatty acid oxidation, muscle fiber type and oxidative enzyme (succinate dehydrogenase) staining activity of muscle.