Abstract: | Objective: To examine the differential response of obesity‐ and diabetes‐related traits to a high‐ or low‐fat diet in LG/J and SM/J mice. We also examined food consumption in these strains. Research Methods and Procedures: Mice were placed on a high‐ or low‐fat diet after weaning. Animals were weighed once per week and subjected to glucose tolerance tests at 20 weeks. At sacrifice, fat pads and internal organs were removed along with serum samples. For food consumption, LG/J and SM/J mice of each sex were assigned to a high‐fat or low‐fat diet after reaching maturity. Mice were weighed three times per week, and food consumed was determined by subtraction. Results: LG/J animals consume more total food, but SM/J animals consume more food per gram of body weight. LG/J mice grow faster to 10 weeks but slower from 10 to 20 weeks, have higher cholesterol and free fatty acid levels, and have lower basal glucose levels and better response to a glucose challenge than SM/J mice. For most traits, SM/J mice respond more strongly to a high‐fat diet than LG/J mice, including body weight and growth, basal glucose levels, organ weights, fat distribution, and circulating triglycerides and cholesterol levels. Discussion: Obesity‐related phenotypes, as well as response to increased dietary fat, differ genetically between LG/J and SM/J and can, therefore, be mapped. This study indicates that the cross of SM/J and LG/J mice would be an excellent model system for the study of gene‐by‐diet interaction in obesity. |