Transgenerational changes of metabolic phenotypes in two selectively bred mouse colonies for different susceptibilities to diet-induced glucose intolerance.
We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.
Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan.
Mototsugu
M
Nagao
Akira
A
Asai
Hitoshi
H
Sugihara
Shinichi
S
Oikawa
D000818:Animals; D001947:Breeding; D015988:Cohort Effect; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D018149:Glucose Intolerance / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010641:Phenotype
D004041:Dietary Fats