Project Number: 1950-51000-061-00
Project Type: Appropriated

Start Date: Oct 01, 2004
End Date: Apr 30, 2009

Objective:
LAB: Energy Metabolism (1) To develop two healthy hypocaloric diets consistent with current dietary recommendations and compare them for their ability to promote long-term CR leading to body weight and fat losses over 1 year in overweight men and women. To test the hypothesis that there are metabolic and anti-aging benefits of long-term (2-year) calorie restriction (CR) in overweight men and women which are equivalent to the benefits seen in animal models, and which result in a delayed rate of biological aging. To quantify the relative associations of different dietary variables (including eating patterns and macronutrient composition), with energy intake and body fatness in free-living young and elderly adults. LAB: Obesity and Metabolism (2) To determine role and molecular mechanisms by which perilipin regulates fat cell lipolysis and fat storage in adipocytes. To determine the mechanism(s) by which the absence of perilipin expression in mouse adipocytes (perilipin null mice) results in resistance to diet and genetic-induced obesity. To define how age, sex, genetic background and diet alters the susceptibility of perilipin null and wild type mice to the development of insulin resistance and diabetes. LAB: Body Composition (3) Adapt newly developed technologies to create, validate and use portable body composition methods for monitoring homebound and institutionalized elderly. Use a new approach to dual energy x-ray absorptiometry to develop a reference method for high precision body composition analysis to replace existing technology, which focuses on bone density measurements. Define the relationship between nutritional status, frailty, cognitive function and hydration status. Validate methods to monitor and manage dehydration and frailty in nursing home elderly. Develop an in vivo whole-body protein status monitor based on minimally invasive fast neutron activation.

Approach:
(1)Obesity and overweight are major public health problems,and are particularly prevalent among elderly adults.The overall goals will be to determine the etiology of weight gain at different adult ages,to develop improved methods for weight loss;and to quantify the potential metabolic benefits and risks of a caloric restriction(CR) program designed to delay biological aging in humans.In particular,a sustainable diet will be developed that can be consumed at 30% less than baseline energy requirements for 1 year and measure its effects on body composition and energy expenditure,and will use that diet to examine the feasibility and metabolic effects of 30%&20% CR over 2 years.In addition,we will analyze national cohort data to identify and quantify the relative effects of different dietary variables on energy intake and body mass index,including dietary fat,dietary glycemic index(GI), dietary fiber and variety.(2)Adipocytes are not only the major repository of body fat,they are also critical regulators of whole lipid body fatty acid flux.Insights into how adipocytes regulate fat metabolism will provide important & necessary info to prevent obesity and its complications.Perilpins(peri) are proteins that coat intracellular stores of fat in adipocytes.Peri act as gatekeepers to regulate fat storage and lipolysis at the lipid droplet surface.While certain details of peri are known,the molecular mechanisms that underlie how peri regulates fat metabolism and the consequences of peri ablation on systemic insulin and glucose homeostasis remain unclear.We will use peri null to delineate the role & molecular mechanisms of peri in regulating adipocyte lipolysis.Peri null mice are resistant to the development of diet-induced & genetic obesity.Investigate potential mechanisms that underlie how peri ablation protects against the development of obesity.Additionally, investigate how different genetic backgrounds,age,% gender interact with peri ablation to alter susceptibility for the development of insulin resistance. (3) Develop & validate a novel portable x-ray absorptiometer and a miniature plasma X-ray fluorescence analysis device to allow accurate field measurements of muscle mass and hydration.Examine the capability of the portable instruments to evaluate body composition in the field by comparing field measurements against established reference methods.Free living elderly as well as nursing home residents will be recruited for these studies, which will also examine the capability of the new instrumentation to monitor hydration,nutritional status,and the efficacy of interventions.Develop & utilize a new fast neutron activation method to study body protein stores and nitrogen balance in vivo and use this methodology to develop guidelines for dietary protein intake.