Leucine supplementation ameliorates early life "programming" of obesity in rats.

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.