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 5weeks 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.