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.
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| 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 |
