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United States Department of Agriculture

Agricultural Research Service

Research Project: THE OBESITY AND ENERGY REGULATION PROGRAM
2012 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. 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.

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 thruoght 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).


4.Accomplishments
1. LAB: Energy Metabolism: The accuracy of calories listed in restaurants. There is little information on the accuracy of information on the calorie contents of commercial foods as provided by the vendors. ARS –funded researchers in the Energy Metabolism Laboratory at the JMUSDA Nutrition Center at Tufts University have conducted a series of studies on the accuracy of published food composition values. Food samples from a variety of restaurant and packaged foods at 3 locations across America (MA, IN, AR) were collected and the samples were analyzed for energy content so that values could be compared to stated values. There was no significant difference between measured and stated values; however, the accuracy of individual stated food energy contents varied widely and foods with low stated energy values contained significantly more energy than stated. In a separate analysis of measured energy data from the national nutrient database (SR-24) a similar finding was reported. These studies highlight the need for more accurate and precise information on the energy contents of different foods, because without such information consumers cannot self-monitor calorie intake to prevent obesity.

2. LAB: Energy Metabolism: Heritability of Body Fatness and Eating Behaviors. There is great uncertainty over the extent to which body weight, body fatness and eating behaviors are heritable. However, such information is important because it helps define the extent to which weight management interventions can be successful, and identifies targets to focus on for behavior changes that can help prevent obesity. ARS–funded researchers in the Energy Metabolism Laboratory at the JM USDA Nutrition Center at Tufts University showed for the first time that the methodology by which body composition is measured has a significant impact on estimates of heritability of body fatness, and that the methods with least bias show that heritability is relatively low. Thus, shared and unique environmental factors are important determinants of an individual’s body fatness. The studies also showed that the eating behavior construct ‘disinhibition’ is not very heritable, suggesting that this variable, which is known to have a significant impact on body fatness, may be susceptible to modification in behavior change programs.

3. LAB: Obesity and metabolism: Immune cells in human fat predict increased fat in liver, abdomen, and altered blood glucose regulation. At the present time we do not understand why some obese people, but not others, have increased abdominal and liver fat and lose the ability to regulate blood glucose. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, in collaboration with University of Southern California Medical School performed fat biopsies on African-American and Hispanic obese young adults and correlated this to other measurements. We found that in both Hispanic and African-American males and females, the presence of specialized cells in fat tissue was associated with accumulation of fat in the liver as well as increased fat tissue within the abdomen. Additionally, we observed that the increase in immune cells in fat tissue correlated with decreased ability to regulate blood glucose. These outcomes provide us with a goal for future nutritional studies to identify food and diets that protect against the increase in immune cells in fat tissue protecting against the development of diabetes and increased fat accumulation in liver and fat.

4. LAB: Body composition: A method to measure energy intake based on stable isotopes and breath samples. Energy intake evaluation is important for the management of obesity. Today, the only available tools for this purpose are based on self-reported food questionnaires which are known to be biased and difficult to apply. ARS researchers at Tufts University in Boston, MA developed an alternative method to measure energy intake, one that is simple enough for field use. After the oral administration of a small amount of fatty acid labeled with a stable carbon isotope (C-13), the appearance of this isotope in breath CO2 is monitored for several days. The rate of clearance depends on the amount of food consumed. Scientists completed a controlled clinical study where volunteers.


Review Publications
Pieper, C., Redman, L., Racette, S., Roberts, S., Bhapkar, M., Rochon, J., Martin, C., Kraus, W., Das, S., Williamson, D., Ravussin, E. 2011. Development of adherence metrics for caloric restriction interventions. Clinical Trials. 8(2):155-164.

Das, S., Roberts, S.B. 2012. Chapter 05: energy metabolism in fasting, fed, exercise and re-feeding states. In: Erdman Jr., J.W., MacDonald, I.A., Zeisel, S.H., editors. Present Knowledge in Nutrition Book Chapter. 10th edition. Hoboken, NJ: Wiley-Blackwell. p. 58-68.

Rickman, A.D., Williamson, D.A., Martin, C.K., Gilhooly, C.H., Stein, R.I., Bales, C.W., Roberts, S.B., Das, S. 2011. The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. Contemporary Clinical Trials. 32(6):874-881.

Pieper, C., Redman, L., Racette, S., Roberts, S., Bhapkar, M., Rochon, J., Martin, C., Kraus, W., Das, S., Williamson, D., Ravussin, E. 2011. Development of adherence metrics for caloric restriction interventions. Clinical Trials. 8(2):155-164.

Elder, S., Roberts, S., Mccrory, M., Das, S., Fuss, P., Pittas, A., Greenberg, A., Heymsfield, S., Dawson-Hughes, B., Bouchard, T., Saltzman, E., Neale, M. 2012. Effect of body composition methodology on heritability estimation of body fatness. Open Nutrition Journal. 6:48-58.

Kelley, G.A., Kelley, K.S., Roberts, S., Haskell, W. 2012. Combined effects of aerobic exercise and diet on lipids and lipoproteins in overweight and obese adults: a meta-analysis. Journal of Obesity. DOI: 10.1155/2012/985902.

Kelley, G., Kelley, K., Roberts, S., Haskell, W. 2012. Comparison of aerobic exercise, diet or both on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Clinical Nutrition. 31(2):156-167.

Racette, S., Das, S., Bhapkar, M., Hadley, E., Roberts, S.B., Ravussin, E., Pieper, C., Delany, J., Kraus, W., Rochon, J., Redman, L. 2012. Approaches for quantifying energy intake and % calorie restriction (CR) during CR interventions in humans: the multicenter CALERIE study. American Journal of Physiology - Endocrinology and Metabolism. 302(4):E441-448.

Das, S., Saltzman, E., Gilhooly, C., Delany, J., Golden, J., Pittas, A., Dallal, G., Bhapkar, M., Fuss, P., Dutta, C., Mccrory, M., Roberts, S. 2009. Low or moderate dietary energy restriction for long-term weight loss: what works best?. Obesity. 17(11):2019-2024.

Beechy, L., Galpern, J., Petrone, A., Das, S. 2012. Assessment tools in obesity- psychological measures, diet, activity, and body composition. Physiology and Behavior. 107(1):154-171.

Shen, W., Patel, S., Miyoshi, H., Greenberg, A.S., Kraemer, F.B. 2009. Functional interaction of hormone-sensitive lipase and perilipin in lipolysis. Journal of Lipid Research. 50(11):2306-2313.

Greenberg, A., Kraemer, F., Soni, K., Jedrychowski, M., Yan, Q., Graham, C., Bowman, T., Mansur, A. 2011. Lipid droplet meets a mitochondrial protein to regulate adipocyte lipolysis. EMBO Journal. 30(21):4337-4339.

Le, K., Mahurkar, S., Alderete, T., Hasson, R., Adam, T., Kim, J., Beale, E., Xie, C., Greenberg, A., Allayee, H., Goran, M. 2011. Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway. Diabetes. 60(11):2802-2809.

Fried, S., Greenberg, A. 2012. Lipocalin 2: a "sexy" adipokine that regulates 17Beta-estradiol and obesity. Endocrinology. 153(4):1582-1584.

De Melo, C.M., Kehayias, J.J., Miyamoto, M.V., Ribeiro, S.M. 2011. Bioelectrical impedance vectorial analysis and nutritional status of older women according to body mass index. Brazilian Journal of Kinanthropometry and Human Performance. 13(6):415-421.

Kehayias, J., Ribeiro, S., Skahan, A., Itzkowitz, L., Dallal, G., Rogers, G., Khodeir, M. 2012. Water homeostasis, frailty and congnitive function in the nursing home. Journal of Nutrition Health and Aging. 16(1):35-39.

Last Modified: 12/24/2014
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