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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

2011 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, 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 two 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) and 1950-51000-071-02S (Regulation of Adipocyte and Adipose Tissue Metabolism in Obesity Related Inflammation and Metabolic Disorders) and 1950-51000-071-03S (Methodology Development: Energy Intake and Body Composition Assessment in the Elderly).

1. LAB: ENERGY METABOLISM. Restaurant-stated calorie contents are broadly accurate with notable exceptions. A study by ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, compared laboratory measurements of calories for 269 food items with the stated calories on restaurant menus and websites. Researchers collected the samples randomly from national fast food restaurants and sit-down chain restaurants in Boston, Massachusetts, Indianapolis, Indiana and Little Rock, Arkansas. On average, the laboratory measurements were only ten calories higher than the restaurants’ stated calories, which broadly supports the wider provision of information on food calorie contents. However, 19% of tested foods contained at least 100 calories more or less than listed, suggesting stated calories for individual foods are often unreliable. The researchers also found that lower calorie food items purchased in sit-down restaurants tended to have more calories than listed. For example, an item purchased as 300 calories and therefore suitable for weight loss or prevention of weight gain typically contained 90 calories more than listed. This study provides important information for consumers on the reliability of information on the calorie content of restaurant foods, and identifies areas where restaurants may improve quality control to provide more accurate information on food energy contents.

2. LAB: ENERGY METABOLISM. Trial of human caloric restriction is feasible. Caloric restriction is the only intervention tested in animal models that reliably increases lifespan. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, are participating in the first multi-site randomized controlled trial of caloric restriction in humans and have published the methodology for conduct of the trial and the intervention. Based on enrollment of human participants in 3 experimental sites and high retention of those subjects through a 2-year study, research studies of human caloric restriction are clearly feasible and will lead to results determining whether caloric restriction has benefits for lifespan and metabolic aging in old age in humans.

3. LAB: OBESITY AND METABOLISM. Factors Identified in Cells that Protect Against Diet-induced Obesity. Since high caloric diets promote obesity in animals and humans ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, identified factors or proteins in cells that will protect against diet-induced obesity. We challenged two different lines of mice with a high caloric diet, one with a lower and the other with a higher expression of the protein, perilipin, in fat cells. They found that mice with increased expression of the protein perilipin in their fat cells (adipocytes) were protected against the development of obesity as compared to mice with reduced expression of perilipin. They demonstrated that increased levels of perilipin in fat cells resulted in increased rates of fat burning and increased levels of proteins that promote burning of fat. These studies indicate that researchers should continue efforts at identifying nutrients and foods that increase perilipin protein expression in fat cells to help ameliorate the epidemic of obesity.

4. LAB: BODY COMPOSITION. A method to gauge frailty. Patients with unwanted weight loss and the elderly are screened for “frailty” using five physiological criteria related to their ability to perform some tasks. This definition provides only a Yes/No result. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, using their newly developed field methods and utilizing data from their studies and a national database, developed a more detailed test that assigns a numerical value to the level of frailty. The impact of this approach is significant. The test requires no cooperation from the subject and because of its numerical outcome, the results can be used to monitor effectiveness of nutritional support and quality of care. The results were published (in press) at the Journal of Nutrition Health and Aging.

Review Publications
Ranjit, S., Boutet, E., Gandhi, P., Prot, M., Tamori, Y., Chawla, A., Greenberg, A., Puri, V., Czech, M. 2010. Regulation of fat specific protein 27 by isoproterenol and TNF-alpha to control lipolysis in murine adipocytes. Journal of Lipid Research. 52(2):221-236.

Orlicky, D.J., Roede, J.R., Bales, E., Greenwood, C., Greenberg, A.S., Petersen, D., Mcmanaman, J.L. 2011. Chronic ethanol consumption in mice alters hepatocyte lipid droplet properties. Alcoholism: Clinical and Experimental. 35(6):1020-1033.

Perfield, J.W., Lee, Y., Shulman, G.I., Samuel, V.T., Jurczak, M.J., Chang, E., Tsichilis, P.N., Obin, M.S., Greenberg, A.S. 2011. Tumor progression locus 2 (TPL2) regulates obesity-associated inflammation and insulin resistance. Diabetes. 60(4):1168-1176.

Kelley, G.A., Kelley, K.S., Roberts, S.B., Haskell, W. 2011. Efficacy of aerobic exercise and a prudent diet for improving selected lipids and lipoproteins in adults: A meta-analysis of randomized controlled trials. BioMed Central (BMC) Medicine. 15;9(1):74.

Sawada, T., Miyoshi, H., Shimada, K., Suzuki, A., Okamatsu-Ogura, Y., Perfield, J., Kondo, T., Nagi, S., Shimizu, C., Yoshioka, N., Greenberg, A., Kimura, K., Koike, T. 2010. Perilipin overexpression in white adipose tissue induces a brown fat-like phenotype. PLoS One. 5(11)e14006.

Grove, K.L., Fried, S.K., Greenberg, A.S., Ziao, X.Q., Clegg, D.J. 2010. mirccroarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice. International Journal of Obesity. 34(6):989-1000.

Meydani, M., Das, S., Band, M., Epstein, S., Roberts, S. 2011. The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the calerie trial of human caloric restriction. Journal of Nutrition Health and Aging. 15:456-460.

Kovsan, J., Bluher, M., Tarnovscki, T., Kloting, N., Kirshten, B., Madar, L., Shai, I., Golan, R., Harman-Boehm, I., Schon, M.R., Greenberg, A., Elazar, Z., Rudich, A. 2011. Altered autophagy in human adipose tissues in obesity. Journal of Clinical Endocrinology and Metabolism. 96(2):E268-277.

Kelley, G.A., Kelley, K.S., Roberts, S.B., Haskell, W. 2011. Efficacy of aerobic exercise and a prudent diet for improving selected lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. BioMed Central (BMC) Medicine. 15; 9(1):74.

Urban, L., Mccrory, M., Dallal, G., Das, K., Saltzman, E., Weber, J., Roberts, S. 2011. Accuracy of stated energy contents of restaurant foods in a multi-site study. Journal of the American Medical Association. 306(3):287-293.

Mccrory, M.A., Howrath, N.C., Roberts, S.B., Huang, T.T. 2011. Eating frequency and energy regulation in free-living adults consuming self-selected diets. Journal of Nutrition. 141:1-6.

Last Modified: 4/15/2014
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