It is the purpose of the proposed study to unravel the differential and interactive influences of genetics, gender and specific life style changes on the development and reduction of the CVD risk directly associated with obesity.
The specific aims of the study are to: isolate the therapeutic potential of a specific aerobic exercise to reduce obesity CVD risk; and quantify the confounding influences of genetics, diet, and gender, alone, and their unique interactions, on the exercise's effect. The therapeutic effect will be quantified by measures of: insulin sensitivity and glucose metabolism, metabolic efficiency of the system, the adverse metabolic correlates of obesity-CVD risk, and lipid metabolism. Animal models are currently necessary to differentiate comparative genetic, gender and environmental influences on obesity-CVD risk development and treatment. The mature fatty Zucker rat (fa/fa) will serve as the genetic model and dietary induced obesity (DIO) will be forced on Sprague-Dawley rats by substituting a high-fat (HF) diet for standard rat chow. Finally, 50% of all fa/fa rats will be fed HF diets to develop a unique genetic-DIO obese, mixed model. These three animal models approximate the many forms of human obesity that exist. Seventy male and 70 females Zucker fa/fa and 60 males and 60 female Sprague-Dawley rats will be used in the study's two phases: 1) obesity-CVD risk development (RD) and 2) low fat, Kcal restrictive diet induced weight reduction (WR). Rats in the exercise group will swim until fatigued, daily, in a large tub, for 6 weeks in both the RD and WR phases of the study. The degree of CVD risk reduction will be measured from behavioral observations and blood and tissue samples. Standard analysis of variance tests will be used to compare and contrast the effects of diet and exercise across the specific animal groups. The differential influences of gender, genetics, diet and exercise on obesity-CVD risk will be assessed via statistical structural modeling techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR004180-05
Application #
6186846
Study Section
Nursing Research Study Section (NURS)
Program Officer
Armstrong, Nell
Project Start
1996-06-11
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2003-03-31
Support Year
5
Fiscal Year
2000
Total Cost
$289,736
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Nursing
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Jarosz, P A; Lennie, T A; Rowsey, P J et al. (2001) Effect of genetic obesity on thermoregulatory activity responses to inversion of the light/dark cycle. Biol Res Nurs 2:249-56
Metzger, B L; Jarosz, P A; Noureddine, S (2000) The effect of a high-fat diet and exercise on the expression of genetic obesity. West J Nurs Res 22:736-48