(P30-003-25) Early-Life Energy Overconsumption and Vitamin A Deficiency Alters Growth, Metabolic Health, and Motor Functions: A Mouse Model of Double-Burden Malnutrition

Objectives: Double burden malnutrition (DBM) is associated with the consumption of energy-dense, nutrient-poor diets and is rising in low- and middle-income countries. The developmental consequences of DBM exposure in utero and during infancy are not fully characterized. The current study utilized a mouse model to investigate the effects of pre- and postnatal exposure to a high-fat, vitamin A (VA)-deficient diet on growth, motor development, and metabolic health.

Methods: C57BL/6J dams (3-5 months of age) were randomly assigned to dietary treatments throughout gestation and lactation. The experimental diets include a VA-replete control diet (CN, 10% fat derived calories), a VA-free control diet (CVD), a VA-replete high-fat diet (HF, 45% fat derived calories), and a VA-free high-fat diet (HVD). Offspring were weaned to the same diet as the dams at 3 weeks of age. Two subsets of pups were subjected to both RotaRod (RR) test for motor function and Grip Strength (GS) test, and euthanized at 3 and 6 weeks of age, respectively. Liver, brain and plasma samples have been submitted for untargeted metabolome analysis. Data were analyzed using one-way ANOVA and Fishers Exact Test analysis was applied for categorical variables.

Results: CN Dams (100%) had higher % breeding success rates than CVD (83.3%), HF (33.33%), and HVD (54.55%). In 6-week pups, both VA deficient groups had lower body weights than CN. The gonadal adipose/body weight ratio was lower in VA deficient groups. Six-week old CN pups had longer tail lengths than all other treatment groups, whereas HVD pups had a greater liver/body weight ratio compared to CVD and CN. At 3 weeks of age, HVD pups had poorer motor coordination with shorter travel distance than CN pups, with no differences detected in sole nutritional burdens. No significance was found in 4-arm GS at 3 or 5 weeks.

Conclusions: The study suggests that gestational exposure to either form (High fat or VA deficiency) or DBM compromises fertility. DBM exerts greater impaired growth, stunted liver health, and impaired motor function in early life compared to sole nutritional burdens. Results from metabolomic analysis will be reported at the conference.

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