1a. Objectives (from AD-416):
LAB: ENERGY METABOLISM 1. Test the feasibility and effectiveness of a long-term caloric restriction intervention program for decreasing body fatness, risk factors for chronic disease, and retarding biological aging. 2. Examine the causes of error in the accuracy of reporting eneergy, macronutrient, and fiber intake from foods. 3. Assess whether a worksite intervention will result in a significant and sustainable reduction in the prevalence of overweight and obese employees and disease risk factors compared to a control group receiving no intervention. 4. Examine the contributions of heritable and environmental factors to eating behaviors and dietary patterns associated with weight gain and body fatness. 5. Assess whether an intervention implemented during pregnancy will result in a significant and sustainable reduction in the prevalence of overweight and obese prior to and subsequent to delivery compared to a control group receiving no intervention. LAB: OBESITY & METABOLISM 1. Define the role and mechanisms of adipocyte death in obesity-associated inflammation and metabolic disorders using genetic and nutritional models of adipocyte growth and death. 2. Determine the role of the macrophage in modulating adipocyte death and associated adipose tissue inflammation using genetically altered animal models. 3. Determine the mechanisms by which alterations in Lipid Droplet (LD) proteins modulate lipolysis and risk of developing metabolic disorders. 4. To determine the role of acyl CoA-synthetase 5 in systemic metabolism. LAB: BODY COMPOSITION 1. Develop and validate mathematical models for carbon kinetics that simulate energy intake, energy regulation, and their relationship to body composition and fat stores. 2. Develop and validate practical field tools for the assessment and management of sarcopenia, dehydration, zinc status and frailty in institutionalized and community living elderly.
1b. Approach (from AD-416):
LAB: ENERGY METABOLISM The etiology and effective prevention of adult-onset weight gain remains poorly understood. In addition, there is little information on the effects of calorie restriction designed to reduce body weight on biological parameters related to aging. These questions will be addressed in a series of 4 studies designed to contribute to understanding the process of dietary change and effective methods for long-term weight control and their effects on long-term health. These will include a randomized controlled trial of human caloric restriction (CALERIE) examining the metabolic effects of a 25% reduction in energy intake for 2 years, a trial of low and high fat diets on weight change in relation to insulin secretion status, a genetic analysis of the heritability of body fat and related parameters in identical twins reared together or reared apart, and an intervention to examine the feasibility of changing dietary Disinhibition in free living individuals and the impact of such a change in body weight. LAB: OBESITY AND METABOLISM The role of adipocyte death in obesity will be investigated using a combination of transgenic and knockout mouse models and bone-marrow transplantation in mice fed different diets to understand the influence of obesity. In vivo and in vitro studies will investigate glucose and insulin homeostasis complemented by histological, immunohistological, electron microscopic, gene expression, FACS analysis, adipocyte lipolysis and Akt signaling studies. For studies investigating lipid droplet proteins, we will use both adenovirus expression vectors and possibly transgenic animals to determine how alterations in expression and intracellular signaling regulate protein expression, metabolic pathways, and lipolysis in cultured cells and animals. Depending upon which tissue is studied, we will examine lipolysis and protein expression, alterations in cytokine, lipid accumulation, signal transduction pathways, and oxidative gene expression. LAB: BODY COMPOSITION Simple monitoring of isotope clearance in breath CO2 can provide quantitative information on average energy intake. Our approach includes the use of a single stable isotope administration (C-13 palmitic acid) and monitoring its disappearance in breath CO2. We will use both mathematical modeling and clinical validation of this approach. The development and validation of new portable body composition tools will include the comparison of a hand-held caliper X-ray absorptiometer against tissue analysis by computerized tomography and the full evaluation of a non-destructive method for rapid analysis of extracellular water by X ray fluorescence analysis for stable bromine. For free-living elderly, we expect that portable body composition tools will provide an additional way to help monitor their medical, functional, and nutritional status so that they can extend safely their independent living.
3. Progress Report:
This progress report includes the work of three subbordinate projects at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-071-01S (Energy regulation during the adult lifespan)and 1950-51000-071-02S (Regulation of adipocyte and adipose tissue metabolism in obesity related inflammation and metabolic disorders) and 1950-51000-071-03S (Methodolgy development: energy intake and body composition assessment in the elderly).
Carpenter, A., Hochstadt, J., Huddleston, J.Y., Kustanovich, V., Reynolds, A.A., Roberts, S.B., Sen, S. 2012. Nutrition, weight gain, and eating behavior in pregnancy: a review of experimental evidence for long-term effects on the risk of obesity in offspring. Physiology and Behavior. 107(1):138-145.