Phase II year
2020
(last award dollars: 2022)
Phase II Amount
$1,569,201
Bariatric surgery has become a common treatment for severe obesity. While this results in the desired loss of fat mass, muscle mass is also lost with implications for post-surgical health benefits. It is our overarching premise that consumption of our essential amino acid (EAA)-based nutritional formulation following bariatric surgery will preserve muscle mass by stimulating muscle protein synthesis. As a result, the energy utilization associated with the combination of maintained muscle mass and stimulated muscle protein synthesis will counter the decrease in metabolic rate that normally occurs in a weight-reduced state. Maintenance of a higher energy expenditure by EAA consumption will accelerate loss of body fat, as well as help maintain weight loss. We further propose that consumption of our EAA-based formulation will reduce muscle lipid accumulation (in the form of both intramyocelluar lipids and intramuscular fat), which will translate to greater improvements in glucose homeostasis and muscle protein metabolism. The following aims will test specific hypotheses related to our scientific premise: Aim 1. Supplementation of the normal diet following bariatric surgery with our proprietary EAA-based formulation twice per day for 6 months will maintain muscle mass and reduce fat mass more than supplementation of the diet with an isonitrogenous amount of whey protein. Muscle mass will be directly measured using a novel tracer-dilution technique using 2H3-creatine. Fat mass and lean body mass will be measured by DEXA. Aim 2. Muscle protein fractional synthetic rate (FSR) and total muscle protein synthesis (muscle mass x FSR) will decline less from pre-surgery values in participants consuming our EAA-based formulation as compared to whey protein. Muscle protein FSR will be measured by the novel virtual biopsy method, which provides an integrated value over two weeks. Aim 3. The pre-surgery rate of total energy expenditure (TEE) will be better maintained in individuals consuming our EAA-based formulation as opposed to whey protein. TEE will be measured over 14-day intervals using the doubly-labeled water technique before and 6-months following surgery. Aim 4. Six months after bariatric surgery both intracellular and intramuscular lipids measured by magnetic resonance spectroscopy and magnetic resonance imaging (MRS/MRI) will be reduced from the pre-surgery levels to a greater extent in participants consuming our EAA-based formulation than whey protein. We anticipate that a greater reduction in these muscle lipid parameters will be related to greater improvement in insulin sensitivity in terms of glucose homeostasis and also in terms of muscle protein synthesis. Positive results of this study will support the value of our EAA-based composition to aid in preservation of muscle mass while facilitating fat loss and improving the likelihood of weight stabilization following bariatric surgery.
Public Health Relevance Statement: 8. Project Narrative Bariatric surgery is an effective treatment for severe obesity but results in loss of muscle mass. We will test the hypothesis that consumption of our essential amino acid-based nutritional formulation will maintain muscle mass while stimulating fat loss after bariatric surgery.
Project Terms: bariatric surgery; base; Base Composition; blood glucose regulation; Body Composition; Body fat; Body Weight decreased; Calories; common treatment; Consumption; Creatine; Data; Diet; Dietary Supplementation; Dilution Techniques; dosage; doubly-labeled water; Dual-Energy X-Ray Absorptiometry; effective therapy; Energy Intake; Energy Metabolism; Essential Amino Acids; Fatty acid glycerol esters; Food; Formulation; Health Benefit; improved; Individual; Industry; insulin sensitivity; Intramuscular; lean body mass; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maintenance; Measurement; Measures; Metabolic; metabolic rate; Methods; Modeling; Morbid Obesity; Muscle; muscle form; Muscle Proteins; Muscular Atrophy; novel; Nutritional; Obesity; Operative Surgical Procedures; Participant; preservation; Protein Biosynthesis; protein metabolism; Proteins; Source; spectroscopic imaging; Supplementation; Techniques; Testing; Time; total energy expenditure; Tracer; Translating; United States; virtual biopsy; Weight; weight loss program; Whey Protein
