Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Division of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Am J Physiol Regul Integr Comp Physiol. 2023 Nov 1;325(5):R576-R592. doi: 10.1152/ajpregu.00137.2023. Epub 2023 Sep 18.
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.
尽管人们积极努力改善围产期营养，但早产儿出生后的生长发育不良仍然是一个重大问题。尽管早产儿出生时体内的钠（Na）稳态经常失调，但维持 Na 稳态对实现最佳生长至关重要。我们假设，在这个关键时期，Na 供应不足会导致生长受限，并为成年后发生心血管代谢疾病带来程序性风险。因此，我们试图确定在生命早期和晚期持续或早期 Na 耗竭对 C57BL/6J 小鼠体重增加、身体成分、食物和水摄入行为以及能量消耗的影响。在一项研究中，3 至 18 周龄的小鼠分别给予低（0.04%）或正常/高（0.30%）-Na 饮食。限制 Na 的小鼠生长缓慢，基础代谢率升高。在第二项研究中，3 至 6 周龄的小鼠给予 0.04%或 0.30%的 Na 饮食，然后在研究结束前恢复到标准（0.15%）-Na 饮食。限制 Na 的小鼠表现出生长延迟，但在恢复到标准饮食后迅速赶上。在 6 至 18 周龄期间，先前限制 Na 的小鼠表现出持续的、程序性的摄食行为变化、总食物摄入量减少、饮水量增加和有氧能量消耗增加，同时保持正常的身体成分。尽管在对照小鼠中没有影响，但给予交感神经阻滞剂六烃季铵可消除先前限制 Na 的小鼠中程序性的基础代谢率增加。这些数据表明，生命早期的 Na 限制会导致摄食行为、自主神经功能和能量消耗的程序性变化，这些变化会持续到成年期。
