Research Project: Energy Regulation and Obesity

Location: Jean Mayer Human Nutrition Research Center On Aging

Project Number: 8050-51000-097-000-D
Project Type: In-House Appropriated

Start Date: Oct 26, 2014
End Date: May 21, 2019

Objective:
ENERGY METABOLISM: 1: Determine the effects of specific dietary composition factors, including macronutrient type, fiber & food form on hunger, satiety & energy regulation. 2: Demonstrate effective methods for sustainable weight control & prevention of obesity in adult population groups spanning a range of ages & demographics. 3: Develop new methodology for improving the accuracy & precision of assessment of energy & nutrient intakes & energy requirements in adults. OBESITY AND METABOLISM: 1: Determine the mechanistic roles of the intestinal and hepatic proteins ACSL5 and plin2 in fatty acid metabolism, especially in delivery of dietary triacylglycerol to tissues and tissue lipogenic metabolism. 2: Determine the physiologic actions and consequences of ACSL5 in diet-induced obesity and obesity associated metabolic complications. BODY COMPOSITION: 1: Develop and validate stable isotope methodology to that can be utilized to investigate energy regulation related to sarcopenic obesity and frailty in the elderly. 2: Validate energy dispersive X-ray fluorescence methodologies for studying the prevalence of zinc deficiency and implications of zinc deficiency in the elderly.

Approach:
LAB NAME: ENERGY METABOLISM The mission of the Obesity and Energetics Laboratory is to understand the effects of lifestyle factors on energy metabolism and weight regulation. Our research examines dietary and behavioral variables that influence both energy intake and metabolism throughout the adult lifecycle, and our focus is to develop and test effective lifestyle interventions for implementing sustainable, healthy weight control at all ages. Studies in our laboratory include in-depth biological examinations of the impact of different dietary factors on biochemical and neurological factors involved in energy regulation and body composition, chemical studies of food composition, and randomized controlled trials testing practical interventions that can be scaled for population-wide benefits. LAB NAME: OBESITY AND METABOLISM To address the role of acyl CoA synthetase 5 (ACSL5) and perilipin 2 (plin2) in intestinal enterocytes and hepatocytes we have generated conditional lines of knockout of ACSL5 and plin2 mice allowing us to disrupt in a tissue specific manner. We will investigate the physiological effects of ablation of ACSL5 and plin2 in mouse hepatocytes and enterocytes and the response to a high caloric diet in vivo. In these animal studies we will determine body composition, energy expenditure, insulin glucose homeostasis, fat absorption, hepatic steatosis, and in liver and intestine tissues gene expression will be determine. In isolated hepatocytes studies in our mice we will triglyceride (TG) accumulation, and TG oxidation. The studies in this project will provide novel insights that will allow researchers to direct therapeutic strategies to protect against the development of obesity and associated complications. LAB: BODY COMPOSITION Simple monitoring of isotope clearance in breath CO2 can provide detailed information on the metabolism of labeled food and help us understand the connection between food composition and energy management. Our approach includes the use of a single stable isotope administration (C-13 palmitic acid or carbohydrate) and monitoring its disappearance in breath CO2 for several days. We use both mathematical modeling and clinical validation. Repeated measurements of C-13 in breath CO2 provide us with a profile of the timing and efficiency of oxidation of the labeled fuel. The development and validation of new tools for field use include a new portable analytical device that can measure zinc content in fingernail clippings. The methodology used is non-destructive energy dispersive X-ray fluorescence (XRF). Preliminary results show that zinc measurement in protein (fingernails) is a better indicator for zinc status than zinc measurements in plasma. This is because plasma values can be easily affected by resent food intake or infection. This methodology will be tested in nursing home residents. It will become an addition to a set of portable devices that we have developed for the evaluation of nutrition status, hydration, and frailty in the field. The instruments are designed to evaluate status as well as to assess the efficacy of treatments and nutrition programs in older adults.