Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada.
J Nutr. 2024 Nov;154(11):3353-3364. doi: 10.1016/j.tjnut.2024.08.031. Epub 2024 Sep 11.
Early nutritional challenges can lead to permanent metabolic changes, increasing risk of developing chronic diseases later in life. Total parenteral nutrition (TPN) is a life-saving nutrition regimen, used especially in intrauterine growth-restricted (IUGR) neonates. Early TPN feeding alters metabolism, but whether these alterations are permanent is unclear. Programmed metabolism is likely caused by epigenetic changes due to imbalances of methyl nutrients.
We sought to determine whether feeding TPN in early life would increase risk of developing dyslipidemia in adulthood and whether supplementing the methyl nutrients betaine and creatine to TPN would prevent this development. We also sought to determine whether IUGR exacerbates the effects of neonatal TPN on lipid metabolism in adulthood.
Female piglets (n = 32; 7 d old) were used in 4 treatments: 24 normal-weight piglets were randomly assigned to sow-fed (SowFed), standard TPN (TPN-control), and TPN with betaine and creatine (TPN-B+C); 8 IUGR piglets were fed control TPN (TPN-IUGR) as a fourth group. After 2 wk of treatment, all pigs were then fed a standard solid diet. At 8 mo old, central venous catheters were implanted to conduct postprandial fat tolerance tests.
Feeding TPN in the neonatal period led to dyslipidemia in adulthood, as indicated by higher postprandial triglyceride (TG) levels in TPN-control (P < 0.05), compared with SowFed. IUGR piglets were particularly sensitive to neonatal TPN feeding, as TPN-IUGR piglets developed obesity and dyslipidemia in adulthood, as indicated by greater backfat thickness (P < 0.05), higher liver TG (P < 0.05), slower postprandial TG clearance (P < 0.05), and elevated fasting plasma nonhigh-density lipoprotein-cholesterol (P < 0.01), and nonesterified fatty acids (P < 0.001), compared with TPN-control.
Feeding TPN in early life increases the risk of developing dyslipidemia in adulthood, especially in IUGR neonates; however, methyl nutrient supplementation to TPN did not prevent TPN-induced changes in lipid metabolism.
早期的营养挑战会导致永久性的代谢变化，增加日后患慢性病的风险。全胃肠外营养（TPN）是一种救命的营养疗法，尤其适用于宫内生长受限（IUGR）的新生儿。早期 TPN 喂养会改变代谢，但这些改变是否是永久性的尚不清楚。程序化代谢可能是由于甲基营养素失衡引起的表观遗传变化所致。
我们旨在确定在生命早期进行 TPN 喂养是否会增加成年后患血脂异常的风险，以及补充 TPN 的甲基营养素甜菜碱和肌酸是否可以预防这种情况的发生。我们还试图确定 IUGR 是否会加剧新生儿 TPN 对成年后脂质代谢的影响。
使用雌性小猪（n = 32；7 天大）进行了 4 种处理：24 只正常体重的小猪被随机分配到母猪喂养（SowFed）、标准 TPN（TPN-control）和 TPN 加甜菜碱和肌酸（TPN-B+C）；8 只 IUGR 小猪作为第四组接受标准 TPN 喂养。治疗 2 周后，所有小猪均开始喂食标准固体饮食。8 个月大时，植入中心静脉导管进行餐后脂肪耐量测试。
在生命早期进行 TPN 喂养会导致成年后血脂异常，TPN-control 组（P < 0.05）餐后甘油三酯（TG）水平升高表明这一点。IUGR 小猪对新生儿 TPN 喂养特别敏感，因为 TPN-IUGR 小猪在成年后会出现肥胖和血脂异常，表现为背部脂肪厚度增加（P < 0.05）、肝 TG 增加（P < 0.05）、餐后 TG 清除速度减慢（P < 0.05）以及空腹血浆非高密度脂蛋白胆固醇（P < 0.01）和非酯化脂肪酸（P < 0.001）升高。
在生命早期进行 TPN 喂养会增加成年后患血脂异常的风险，尤其是在 IUGR 新生儿中；然而，TPN 中补充甲基营养素并不能防止 TPN 引起的脂质代谢变化。
