(P10-008-23) Maternal Low Protein Diet Influence on Transgenerational Metabolic Syndrome in the Collaborative Cross

Objectives: Child and maternal health are compromised when there is inadequate access to comprehensive nutrition. Gestation plays a crucial role in a child’s predisposition towards developing cardiometabolic diseases. The effects of maternal diet have not been fully examined in the context of maternal genetics and experiments in genetic reference panels from model organisms may aid our understanding of genetic influence on gene:diet interactions during gestation. This study examineshow a maternal low protein (LP) diet influences the Metabolic syndrome (MetSyn) phenotypes of offspring in Collaborative Cross (CC) mice.

Methods: The following three CC strains, a multiparental recombinant inbred panel emulating a genetically reproducible heterogeneous population, were selected: CC001, CC0019, and CC040. The CC dams were randomly placed on a 5-week dietary intervention with either the control synthetic AIN-93G diet or the experimental LP diet. After two weeks, CC males were introduced for reciprocal cross (AxB, BxA, AxC, CxA, BxC, and CxB) breeding. Approximately 21 days later, when pups were born, all dams were placed on AIN-93G diet as they weaned offspring. During pup’s 4th and 8th weeks, their body composition and weight were recorded. Adiposity was measured via an EchoMRI. Body fat percent (BF%) was calculated by dividing fat mass by total weight. Data were analyzed using unpaired T-tests.

Results: Among all reciprocal crosses the effect of maternal diet on offspring body weight (BW) and BF%, at weeks 4 and 8, is not statistically different (p > 0.05, p > 0.50, and p > 0.50, p > 0.50). However, there were significant differences within reciprocal cross for both BW and BF%. For example, at weeks 4 and 8 on both diets, the CC019xCC001 cross had greater BF% than the CC001xCC019 cross. Intriguingly, at week 8 on both diets, the CC001xCC019 cross is heavier yet the CC019xCC001 cross has a greater BF%. The diet effect was variable between strains and reciprocal crosses indicating that genetic susceptibility is an important determinant of gestational nutrient need.

Conclusions: The genetic variance between the CC strains, and parent of origin genetics, have important effects on the metabolic health of offspring. The effect of diet is also likely dependent on the underlying maternal genetics. 

Funding Sources: This research was supported by a National Institute of Food and Agriculture grant.