290 - Low Sodium Supply in Early Life Causes Growth Restriction and Programs Long-Term Changes in Energy Homeostasis

Poster Number: 290
Publication Number: 290.120

Alisha A. Ziegler, Medical College of Wisconsin, Milwaukee, WI, United States; Connie Grobe, Medical College of Wisconsin, Brookfield, WI, United States; John J. Reho, Medical College of Wisconsin, Milwaukee, WI, United States; Justin L. Grobe, Medical College of Wisconsin, Milwaukee, WI, United States; Jeffrey L. Segar, Medical College of Wisconsin, Brookfield, WI, United States

Background: Postnatal growth failure in preterm infants remains a significant morbidity and predisposes infants to significant life-long risk of neurologic and cardiometabolic morbidities. Studies in animals and humans suggest early life sodium (Na) depletion may contribute to growth failure. Although mechanisms contributing to the development of Na depletion in preterm infants are generally understood, the mechanisms by which such Na depletion impacts somatic growth and energy expenditure remain unclear.

Objective: Exploit newly developed mouse models of early life Na depletion to understand mechanisms by which Na homeostasis regulates growth, body composition and metabolism.

Design/Methods: : Male C57BL/6J mice were placed on low (0.04% Na), or normal/high (0.3% Na) soy-free chow at weaning (PD21 / age 3 weeks) for three weeks (to PD42 / age 6 weeks), then returned to 0.15% Na until study completion. Body mass, body composition, food and water intake, physical activity and energy expenditure were serially assessed using time-domain nuclear magnetic resonance (Bruker NMR) and multiplexed metabolic phenotyping (Promethion, Sable Systems). Data were analyzed using Generalized Linear Modeling (GLM) methods to account for covariates such as body composition and food intake behavior.

Results: : Mice provided low-Na from P21-P42 demonstrated growth restriction with a rapid catch-up growth upon return to standard 0.15% Na diet and similar growth kinetics to the 0.3% Na group thereafter. Differences in body mass related to decreased fat-free (diet x age interaction p < 0.01), but not fat mass. Mice fed low-Na diet exhibited reduced food intake but increased water intake (both (p < 0.01) at all timepoints to study conclusion (18 weeks) even after correction for body composition. Mice fed 0.04% Na diet also exhibited a very large (≈5%) increase in aerobic energy expenditure that was sustained (i.e. programmed) for at least 3 months after return to 0.15% Na diet (p < 0.01); this effect being sustained even after correction for body composition and food intake.Conclusion(s): Mice exposed to low Na supply in early life demonstrate physiologically / pathophysiologically significant changes in growth, energy consumption and expenditure that are programmed to last in to adulthood. These findings support our hypothesis that early-life Na supply impacts energy homeostasis and growth kinetics and suggest the provision of sufficient Na to premature infants early in life will promote growth and may be necessary to optimize long term health.