Distinct phenotypes of obesity-prone AKR/J, DBA2J and C57BL/6J mice compared to control strains

Abstract

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 high-calorie diets. 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. 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 (<40%). 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. 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.