Effects of Soy Protein Isolate on Fragile X Phenotypes in Mice

Obesity is a pediatric epidemic that is more prevalent in children with developmental disabilities. We hypothesize that soy protein-based diets increase weight gain and alter neurobehavioral outcomes. Our objective herein was to test matched casein- and soy protein-based purified ingredient diets in a mouse model of fragile X syndrome, Fmr1 mice. The experimental methods included assessment of growth; 24-7 activity levels; motor coordination; learning and memory; blood-based amino acid, phytoestrogen and glucose levels; and organ weights. The primary outcome measure was body weight. We find increased body weight in male Fmr1 from postnatal day 6 (P6) to P224, male wild type (WT) from P32-P39, female Fmr1 from P6-P18 and P168-P224, and female Fmr1 from P9-P18 as a function of soy. Activity at the beginning of the light and dark cycles increased in female Fmr1 and Fmr1 mice fed soy. We did not find significant differences in rotarod or passive avoidance behavior as a function of genotype or diet. Several blood-based amino acids and phytoestrogens were significantly altered in response to soy. Liver weight was increased in WT and adipose tissue in Fmr1 mice fed soy. Activity levels at the beginning of the light cycle and testes weight were greater in Fmr1 versus WT males irrespective of diet. DEXA analysis at 8-months-old indicated increased fat mass and total body area in Fmr1 females and lean mass and bone mineral density in Fmr1 males fed soy. Overall, dietary consumption of soy protein isolate by C57BL/6J mice caused increased growth, which could be attributed to increased lean mass in males and fat mass in females. There were sex-specific differences with more pronounced effects in Fmr1 versus WT and in males versus females.