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United States Department of Agriculture

Agricultural Research Service

Research Project: The Obesity and Energy Regulation Program

Location: Human Nutrition Research Center on Aging

2010 Annual Report


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.

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.

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 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 project includes the work of three subordinate 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), 1950-51000-071-02S (Regulation of Adiposity and Adipose Tissue Metabolism in Obesity Related Inflammation and Metabolic Disorders), 1950-51000-071-03S (Methodology Development: Energy Intake and Body Composition Assessment in the Elderly).


4.Accomplishments
1. The stated energy contents of packaged foods and restaurant meals are frequently inaccurate. (LAB: Energy Metabolism). This topic has become an important public health issue with the issuance of new government directions to increase information available to consumers and increasinginterest in ways to help individuals control their weight. If information is to be provided to consumers, the information should be accurate so that values provided are not misleading. ARS funded researchers from Tufts University in Boston, MA examined the accuracy of reported energy values in packaged frozen meals and restaurant foods in the Greater Boston area by collecting a convenience sample of foods and measuring energy content by adiabatic bomb calorimetry. We found that there was substantial variability in the accuracy of reported energy contents that far exceeded the measurement error for dietary energy, and on average both package foods and restaurant meals tended to have more energy than reported. Results from this study will improve accuracy of information provided to the public with regard to calorie content of food, which will help in making better food choices and in reducing the burden of obesity.

2. Moderate-energy-restriction diets result in more consistent weight control compared to low-energy restriction diets. (LAB: Energy Metabolism). We examined whether low or moderate energy restriction might be most effective for sustainable weight control. ARS funded researchers from Tufts University in Boston, MA studied 46 overweight men and women who were recommended to follow a diet with either 10% or 30% reduced energy for 1 year. There was no significant difference in weight or body fat loss between the two groups, but greater variability in weight loss in the 10% group, indicating that low energy restriction is effective for weight control in some individuals but not in others. These results demonstrate for the first time that the optimal level of energy restriction for effective weight control may differ between individuals and that, contrary to previous speculation, low-energy restriction does not appear to be more successful long-term than moderate-energy restriction.

3. A low dietary glycemic load diet prevents emergence of subclinical depression during weight loss. (LAB: Energy Metabolism). The question of whether dietary composition influences mood and cognition has been controversial because most previous studies have not provided food (through controlled diet), or have been conducted for only short periods of time. ARS funded researchers at Tufts University in Boston, MA assessed the effects of dietary glycemic load on mood and cognition in 39 adults undergoing a caloric restriction program for 1 year. During the first 6 months of the program, when all food was provided, a rise in subclinical symptoms of depression occurred in the subjects randomized to a high glycemic load diet versus no such change in the subjects randomized to a low glycemic load diet, indicating that consumption of a low glycemic load diet was protective against negative affect during weight loss. This study, due to its long-term provision of food of carefully controlled composition, provides the first evidence that dietary carbohydrate/fat balance in the diet can influence mood.

4. Heritability and the environment affect lipid risk factors for cardiovascular diseases. (LAB: Energy Metabolism). The heritability of lipid risk factors for cardiovascular disease is uncertain. ARS funded researchers from Tufts University studied the heritability of lipid parameters in a rare population of adult identical twins reared apart, to examine heritability. We found significant heritability of all lipid parameters but also substantial environmental contribution to each parameter. These findings emphasize the importance of the environment in health risk factors for cardiovascular disease in adults.

5. Estrogen increases skeletal muscle’s ability to burn fat. (LAB: Obesity and Metabolism). When women stop producing estrogen during the transition to menopause they are at an increased risk of developing obesity; however, the protective anti-obesity actions of estrogen are poorly understood. ARS-funded researchers from Tufts University in Boston, MA compared the characteristics of skeletal muscle in female mice that have lost the ability to produce estrogen as compared to female mice which produce estrogen normally. Our studies demonstrated that estrogen acts on muscle to produce a group of proteins that enhances the ability of muscle to burn fat. The results of this study demonstrate an important mechanism by which estrogen functions in women to protect against the development of obesity. Importantly this observation will direct researchers to investigate and identify nutrients that will mimic estrogen’s actions on skeletal muscle to facilitate fat burning.

6. A rapid and inexpensive method to determine de-hydration and frailty. (LAB: Body Composition). ARS-funded researchers from Tufts University in Boston, MA have proven the feasibility of measuring extracellular water space in the field using miniaturized equipment. The method replaces traditional neutron activation analysis for plasma bromine, which requires access to a nuclear reactor, or high-performance liquid chromatography (HPLC), which requires extensive sample preparation in the laboratory. Using our non-destructive X-ray technique, the plasma specimen can be analyzed in its original plastic container without opening the vial or contaminating the sample. The method provides a rapid way to determine de-hydration and frailty in nursing homes. Dehydration is a major cause of hospitalization of nursing home residing elderly. This method will make possible the early detection of dehydration and protect the elderly from its compilations.


Review Publications
Urban, L., Dallal, G.E., Robinson, L., Ausman, L., Saltzman, E., Roberts, S.B. 2010. The accuracy of stated energy contents of reduced-energy, commercially Prepared Foods. American Dietetic Association. 110:116-123.

Shaul, M.E., Bennett, G., Strissell, K.J., Greenberg, A.S., Obin, M. 2010. Dynamic M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high fat diet-induced obesity in mice. Diabetes. 59(5):1171-1181.

Sapiro, J.M., Mashek, M.T., Greenberg, A.S., Mashek, D.G. 2009. Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor alpha activity. Journal of Lipid Research. 50(8):1621-1629.

Defuria, J., Bennett, G., Strissel, K.J., Milbury, P.E., Perfield, J.W., Greenberg, A.S., Obin, M. 2009. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. Journal of Nutrition. 139(8):1510-1516.

Miyoshi, H., Souza, S.C., Endo, M., Sawada, T., Perfield, J.W., Shimizu, C., Stancheva, Z., Nagai, S., Strissel, K.J., Yoshioka, N., Obin, M.S., Koike, T., Greenberg, A.S. 2010. Perilipin overexpression in mice protects against diet-induced obesity. Journal of Lipid Research. 51(5):975-982.

Rogers, N.H., Perfield, J.W., Strissel, K.J., Obin, M.S., Greenberg, A.A. 2010. Ovarian function in mice results in abrogated skeletal muscle PPARdelta and FoxO1-mediated gene expression. Biochemical and Biophysical Research Communications. 392:1-3.

Schlosser, K., Taylor, J., Kehayias, J., Tegenkamp, M.H., Schoeller, D.A. 2009. In vivo and in vitro bromide equilibration time course in adults and sample handling effect. International Journal of Body Composition Research. 7:141-147.

Last Modified: 4/17/2014
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