Early-life sodium deprivation programs long-term changes in ingestive behaviors and energy expenditure in C57BL/6J mice.

Postnatal growth failure remains a significant problem for infants born prematurely, despite aggressive efforts to improve perinatal nutrition. Though often dysregulated in early life when children are born preterm, sodium (Na) homeostasis is vital to achieve optimal growth. We hypothesize that insufficient Na supply in this critical period contributes to growth restriction and programmed risks for cardiometabolic disease in later adulthood. Thus, we sought to ascertain the effects of prolonged versus early-life Na depletion on weight gain, body composition, food and water intake behaviors, and energy expenditure in C57BL/6J mice. In one study, mice were provided a low (0.04%)- or normal/high (0.30%)-Na diet between 3 and 18 wk of age. Na-restricted mice demonstrated delayed growth and elevated basal metabolic rate. In a second study, mice were provided 0.04% or 0.30% Na diet between 3 and 6 wk of age and then returned to standard (0.15%)-Na diet through the end of the study. Na-restricted mice exhibited growth delays that quickly caught up on return to standard diet. Between 6 and 18 wk of age, previously restricted mice exhibited sustained, programmed changes in feeding behaviors, reductions in total food intake, and increases in water intake and aerobic energy expenditure while maintaining normal body composition. Although having no effect in control mice, administration of the ganglionic blocker hexamethonium abolished the programmed increase in basal metabolic rate in previously restricted mice. Together these data indicate that early-life Na restriction can cause programmed changes in ingestive behaviors, autonomic function, and energy expenditure that persist well into adulthood.

Sodium and Growth in Preterm Infants: A Review.

Aim: This article is intended to review the relationship between sodium homeostasis and growth, outline reasons why preterm infants may become sodium deficient, and share data from our group and others regarding the potential benefits of dietary sodium supplementation. Background: Despite tremendous efforts over the past 20 years to optimize neonatal nutrition, postnatal growth failure in preterm infants remains a significant problem. Compelling associations have been identified between in-hospital growth failure and cardiometabolic and neurodevelopmental disorders, heightening the need to further identify the optimal nutritional needs of preterm infants. Results: The impact of sodium deficiency may have on somatic growth is poorly studied and reported upon within the human literature. In contrast, animal studies dating back almost 100 years highlight the nutritional importance of dietary sodium. Sodium homeostasis during early postnatal life is understudied and underappreciated by neonatologists. Conclusion: Insufficient sodium intake during early life is likely a critical yet underappreciated contributor to growth failure. Total body sodium depletion may be an important risk factor driving complications of premature birth. Clinical significance: Increased awareness of sodium homeostasis in preterm infants may improve outcomes in this population. Sodium intake recommendations are provided based on the interpretation of currently available literature.

Cardiometabolic Effects of DOCA-Salt in Mice Depend on Ambient Temperature.

BACKGROUND: Mice prefer warmer environments than humans. For this reason, behavioral and physiological thermoregulatory responses are engaged by mice in response to a standard room temperature of 22 to 24 °C. Autonomic mechanisms mediating thermoregulatory responses overlap with mechanisms activated in hypertension, and, therefore, we hypothesized that housing at thermoneutral temperatures (TNs; 30 °C) would modify the cardiometabolic effects of deoxycorticosterone acetate (DOCA)-salt in mice. METHODS: The effects of DOCA-salt treatment upon ingestive behaviors, energy expenditure, blood pressure, heart rate (HR), and core temperature were assessed in C57BL/6J mice housed at room temperature or TN. RESULTS: Housing at TN reduced food intake, energy expenditure, blood pressure, and HR and attenuated HR responses to acute autonomic blockade by chlorisondamine. At room temperature, DOCA-salt caused expected increases in fluid intake, sodium retention in osmotically inactive pools, blood pressure, core temperature, and also caused expected decreases in fat-free mass, total body water, and HR. At TN, the effects of DOCA-salt upon fluid intake, fat gains, hydration, and core temperature were exaggerated, but effects on energy expenditure and HR were blunted. Effects of DOCA-salt upon blood pressure were similar for 3 weeks and exaggerated by TN housing in the fourth week. CONCLUSIONS: Ambient temperature robustly influences behavioral and physiological functions in mice, including metabolic and cardiovascular phenotype development in response to DOCA-salt treatment. Studying cardiometabolic responses of mice at optimal ambient temperatures promises to improve the translational relevance of rodent models.

Short-term Housing in Metabolic Caging on Measures of Energy and Fluid Balance in Male C57BL/6J Mice ( Mus musculus).

Metabolic caging is an important tool for quantitative urine and feces collection in rodents, although significant limitations and problems accompany its use. Despite strong opinions among investigators regarding the effects of metabolic caging on energy and fluid homeostasis, careful quantitative analysis of the impact of this caging type-particularly when used for mice-is lacking. The current study assessed the effects of metabolic caging, with or without modifications such as plastic platform inserts, on ingestive behaviors, energy expenditure, accuracy of urine and fecal collection, and ambulatory activities in male C57BL/6J mice. Housing mice in metabolic cages, regardless of platform inclusion, increased energy expenditure without modifying food intake, presumably due to the inability of mice to perform normal thermoregulatory behaviors (burrowing and huddling). Surprisingly, mice in metabolic cages actively avoided platforms, and the inclusion of platforms modified the behavior of the mice and had position-dependent effects that reduced the accuracy of urine collection. Moving mice from cohousing to individual housing in home cages also increased ingestive behaviors and energy expenditure. We conclude that single housing of male C57BL/6J mice increases energy expenditure, that this increase is potentiated in metabolic caging conditions, and that platforms in metabolic cages alter mouse behavior and urine collection. Additional future work is needed to determine the potential benefits of using higher ambient temperature for studies of mice in metabolic caging and whether the above effects occur in females and other strains of mice and other rodent species.