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Objective: To investigate the difference between obesity prone (OP) and obesity resistant (OR) phenotypes in the homeostatic regulation of energy balance.Methods: Sixty male Sprague Dawley (SD) rats were selected to establish the OP and OR rat models by free accessing to a high-fat diet for 15 wk.Then one-half of the rats in each group (OP, OR and Control) were placed on a food restriction schedule and allowed access to 50% of their individual baseline mean daily food intake each day, while the other half were maintained on ad libitum food for 2 wk.Body weight, body length, serum lipid levels, energy intake, basal metabolic rate (BMR), resting metabolic rate (RMR) and body composition were measured in OP and OR rats either in high-fat diet ad libitum condition or diet restrict feeding state.Results: The results showed that in high-fat diet ad libitum condition there was no significant differences in energy intake among the OP, OR and control group during this period.The OP group showed a significant higher feeding efficiency than that in OR and control.BMR and RMR for OR was significantly higher than the other two groups, while BMR for OP was a little lower than that of Control group.50% Diet restriction led to a reduction in BMR and RMR in all groups compared with ad libitum feeding state;OR rats showed a significantly greater reduction in BMR and RMR.The OP group showed a significant decrease in body fat weight and fat content during the food restriction period, while there was no significant differences in OR rats.Conclusion: There are significant differences between OP and OR rats in BMR either in HFD ad libitum condition or diet restrict feeding state.OR rat has the ability to sense and respond to energy imbalance accurately while the system in OP is blunted.OR rat has the ability to sense and respond to energy imbalance accurately while the system in OP is blunted.