The major barrier to successful obesity treatment is the inability, in most people, to maintain weight loss over time. The investigators propose to use a well-established rat model of high fat diet (HFD)-induced dietary obesity to study barriers to maintenance of reduced body weight. The investigators believe that this model will allow them to identify rats most (obesity prone or OP) and least (obesity resistant or OR) susceptible to dietary obesity. They propose to study OP rats in the reduced-obese state after a period of dietary obesity in order to identify the contribution of the reduced-obese metabolic state to weight regain. The metabolic state will be defined by a) energy expenditure per unit of fat-free mass (FFM), b) the proportion of total energy expenditure from fat oxidation, c) the changes in energy expenditure and fat oxidation in response to acute dietary challenges (i.e. under- and overfeeding).
Specific aims of the proposal are: 1) to determine why and to what extent the metabolic state of the reduced-obese OP rat contributes to weight regain, and whether this metabolic state is partially or completely reversed with sustained weight maintenance; 2) To determine why and to what extent exercise prevents weight regain in reduced-obese OP rates. Two studies are proposed to accomplish the proposed specific aims. Both studies involve assessing the metabolic state of OP rats before HF-feeding (pre-obese state), during HFD-feeding (obese state) and following weight reduction by restriction of a low fat diet (reduced-obese state). OR rats will be subjected to similar conditions. In Study 1, reduced-obese OP rats will be studied at three time points during a 16- week weight maintenance period in order to assess the constancy of the reduced-obese metabolic state. The investigators will compare the reduced-obese metabolic state of reduced-obese OP rats with the metabolic state seen in their pre-obese condition. The investigators propose to compare OP to OR rats and to a group of OP controls, fed a LFD throughout. In study 2, exercise (at 1 hr/d or 2/hr/d) will be used in reduced-obese OP rats to assess its impact upon weight regain and the reduced-obese metabolic states. The investigators have previously identified physiological pathways that differ between OP and OR rats before and during HFD feeding. In both studies, they will assess these pathways in order to determine potential mechanisms underlying the reduced-obese metabolic state. The results of these studies will help determine the extent to which metabolism in the reduced-obese state contributes to weight regain, whether this state is reversible over time and which physiological mechanisms are responsible for this metabolic state.
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