Selective breeding of mice for different susceptibilities to high fat diet‐induced glucose intolerance: Development of two novel mouse lines, Selectively bred Diet‐induced Glucose intolerance‐Prone and ‐Resistant

Aims/Introduction: The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet‐induced diabetes, we performed selective breeding for differences in high fat diet (HFD)‐induced glucose intolerance. Materials and Methods: Selective breeding was performed using hybrid mice of C57BL/6J, C3H/HeJ and AKR/N backgrounds. After 5‐week HFD feeding, mice showing high and low 2‐h blood glucose levels in an oral glucose tolerance test (OGTT) were selected and bred over 14 generations to produce lines prone and resistant to diet‐induced glucose intolerance (designated Selectively bred Diet‐induced Glucose intolerance‐Prone [SDG‐P] and ‐Resistant [SDG‐R]). Results: At 5 weeks of age (pre HFD feeding), SDG‐P mice showed higher blood glucose levels both in the OGTT and insulin tolerance test as compared to SDG‐R mice. After receiving HFD, the glucose intolerance of SDG‐P mice became more evident without hyper insulin secretion. In addition, SDG‐P mice had greater body weight gain and lower HDL‐cholesterol levels as compared to SDG‐R mice. In comparison with C57BL/6J, a well‐known strain prone to HFD‐induced glucose intolerance, SDG‐P mice showed significantly higher glucose levels in OGTT after the 5‐week HFD feeding. Conclusions: Susceptibility to HFD‐induced glucose intolerance was transmitted over generations and was intensified by selective breeding. The newly established mouse lines, SDG‐P and SDG‐R, may be useful in investigating the pathophysiology of type 2 diabetes through elucidating the crucial factors for determining the susceptibility to HFD‐induced glucose intolerance. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00175.x, 2011)