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Objective: To characterize and compare three obesity-prone inbred strains, AKR/J, DBA/2J and C57BL/6J, to three control strains, C3H/HeJ, BALB/cByJ and C57L/J, selected based on their normal eating patterns and moderate weight gain on highcalorie diets. Methods and procedures: These six strains were examined at 5 weeks of age while still of normal body weight, and they were maintained for 1 day or 3 weeks on different feeding paradigms with macronutrient diets. Measurements were taken of macronutrient intake, body weight and body fat accrual, circulating hormones and metabolites, and the hypothalamic peptide, galanin. Results: The three control strains each selected a balanced diet with 50% carbohydrate and 15-25% fat when given a choice of macronutrients, and they had similar, normal range of scores for the measures of body weight, adiposity, the hormones, insulin and leptin, and the metabolites, glucose and triglycerides. When compared to this control baseline, the obesity-prone strains with similar total caloric intake to controls selected a diet with significantly more fat (30-40%) and less carbohydrate (o40%). They also had greater adiposity, with the largest differences detected for the AKR/J and DBA/2J strains. These two obesity-prone strains compared to control strains had elevated levels of insulin and leptin. They also had higher triglyceride levels and increased expression and levels of galanin in the hypothalamic paraventricular nucleus. A very different pattern was detected in the obesity-prone C57BL/6J strain, which exhibited a stronger preference for protein as well as fat, normal levels of insulin, leptin and triglycerides, hyperglycemia relative to all other strains, and a small increase in galanin. Conclusion: These comparisons to control strains revealed a distinct phenotype in the two obesity-prone strains, AKR/J and DBA/2J, which is very similar to that described in obesity-prone, outbred rats. They also identified a clearly different phenotype in the obesity-prone C57BL/6J strain.

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Patterns of eating behavior, body weight gain, and hormone changes were examined in normal-weight albino Sprague-Dawley rats on macronutrient diets. These diets consisted of either three separate jars with pure macronutrients, fat, carbohydrate and protein, from which to choose, or a single diet with different concentrations of fat and carbohydrate. Similar patterns on the choice-diet and single-diet paradigms were observed. During the first 7–10 days on these diets but not subsequently, the rats consuming a fat-rich diet exhibit significant hyperphagia, an increase in both total and fat intake that produces higher body weight gain. Compared with a 10% fat diet, a 30% fat diet is associated with a decline in insulin and corticosterone (CORT) levels, whereas a 60% fat diet produces an increase in circulating glucose. Levels of glucose are positively correlated with fat intake, and together these measures are consistently related to body fat. These relationships are most strongly expressed in rats that consume a fat-rich diet with >30% fat. Whereas insulin levels are also positively related to body fat, CORT is inversely related in these normal-weight subjects. In animals consuming a high-fat diet, a clear separation can be seen between “obesity-prone” (OP) rats with 100% greater body fat than “obesity-resistant” (OR) rats. The OP rats, which consume 15% more total calories, have significantly higher insulin and glucose levels. In animals that consume a diet with >30% fat, it is the OP but not the OR rats that exhibit a positive relation between fat intake, glucose levels, and body fat and reveal an additional association between carbohydrate intake, insulin, and body fat. Thus these rats on macronutrient diets exhibit distinct traits that relate behavior to hormone disturbances and adiposity and distinguish subjects that are prone vs. resistant to obesity.