Effects of Soy Protein Isolate on Fragile X Phenotypes in Mice

Abstract

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, Fmr1KO 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 Fmr1KO from postnatal day 6 (P6) to P224, male wild type (WT) from P32–P39, female Fmr1KO from P6–P18 and P168–P224, and female Fmr1HET from P9–P18 as a function of soy. Activity at the beginning of the light and dark cycles increased in female Fmr1HET and Fmr1KO 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 Fmr1KO mice fed soy. Activity levels at the beginning of the light cycle and testes weight were greater in Fmr1KO versus WT males irrespective of diet. DEXA analysis at 8-months-old indicated increased fat mass and total body area in Fmr1KO females and lean mass and bone mineral density in Fmr1KO 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 Fmr1KO versus WT and in males versus females.

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

“…The control diet in both studies was AIN-76A, which was matched for vitamin and mineral content with the KD; however, mice were transferred from the standard vivarium chow (2019 Teklad Global 19% Extruded Rodent Diet) to AIN-76A or KD at P18 in the prior study [ 43 ] and P95 here. The longer maintenance time on the chow could account for the altered sleep phenotype, as purified-ingredient diets have been shown to reduce seizure propensity, body weight, and lean mass in mice compared to chows [ 53 , 54 , 55 ], which could mask genotype differences. Reduced sleep in Fmr1 KO mice compared to WT on the control diet during the middle of the light cycle overlaps with published actigraphy data in mice undergoing a similar KD treatment protocol, where Fmr1 KO mice exhibit a 38% increase in activity during the first half of the light cycle (Figure 3E in [ 4 ]).…”