The advanced cessation of lactation elevates the risk of programmed obesity and obesity-related metabolic disorders in adulthood. The study used multi-omics analysis to investigate the mechanism behind this phenomenon and the effects of leucine supplementation on ameliorating programmed obesity development. Wistar/SD rat offspring were subjected to early weaning (EW) at d 17 (EWWIS and EWSD groups) or normal weaning at d 21 (CWIS and CSD groups). Half rats from the EWSD group were selected to create a new group with two-month leucine supplementation at d 150. The results showed that EW impaired lipid metabolic gene expressions and increased insulin, neuropeptide Y, and feed intake, inducing obesity in adulthood. Six lipid metabolism-related genes (Acot1, Acot2, Acot4, Scd, Abcg8, and Cyp8b1) were influenced by EW during the whole experimental period. Additionally, adult earlyweaned rats exhibited cholesterol and fatty acid β-oxidation disorders, liver taurine reduction, cholestasis, and insulin and leptin resistance. Leucine supplementation partly alleviated these metabolic disorders and increased liver L-carnitine, retarding programmed obesity development. This study provides new insights into the mechanism of programmed obesity development and the potential benefits of leucine supplementation, which may offer suggestions for life planning and programmed obesity prevention.

中文翻译：

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补充亮氨酸可改善大鼠生命早期的肥胖“编程”

提前停止哺乳会增加成年后程序性肥胖和肥胖相关代谢紊乱的风险。该研究利用多组学分析来研究这种现象背后的机制以及补充亮氨酸对改善程序性肥胖发展的影响。Wistar/SD 大鼠后代在第 17 天（EWWIS 和 EWSD 组）进行早期断奶（EW），或在第 21 天（CWIS 和 CSD 组）进行正常断奶。从 EWSD 组中选择一半大鼠，创建一个新组，在第 150 天补充两个月亮氨酸。结果表明，EW 损害脂质代谢基因表达，增加胰岛素、神经肽 Y 和采食量，诱发成年期肥胖。在整个实验期间，6个脂质代谢相关基因（Acot1、Acot2、Acot4、Scd、Abcg8和Cyp8b1）受到EW的影响。此外，成年早期断奶大鼠表现出胆固醇和脂肪酸β-氧化紊乱、肝脏牛磺酸减少、胆汁淤积以及胰岛素和瘦素抵抗。补充亮氨酸可部分缓解这些代谢紊乱并增加肝脏左旋肉碱，从而延缓程序性肥胖的发展。这项研究为程序性肥胖发生的机制和补充亮氨酸的潜在益处提供了新的见解，可能为生活规划和程序性肥胖预防提供建议。