Leptin Supplementation During Lactation Restores Key Liver Metabolite Levels Malprogrammed by Gestational Calorie Restriction.

SCOPE: Perinatal nutritional factors can program offspring metabolic phenotype and risk to obesity. We investigated the potential role of leptin supplementation (during lactation) in ameliorating the malprogrammed effects caused by mild maternal calorie restriction during gestation, on young rat offspring liver metabolic response.

METHODS AND RESULTS: Untargeted and targeted metabolomics studies on liver samples were performed by NMR and GC-MS, respectively. Global DNA methylation and the expression by RT-PCR of key genes involved in different pathways were also determined. By NMR, fifteen liver metabolites were observed to be altered in the offspring of gestational calorie-restricted dams (CR group), at days 25-27 of life. Physiological leptin supplementation during lactation partially reverted the effect of CR condition for most of these metabolites. Moreover, targeted fatty acid analysis by GC-MS showed a significant decrease in the hepatic concentration of certain very long-chain fatty acids (VLCFA) in CR offspring, partially or totally reverted by leptin supplementation. No remarkable changes were found in global DNA methylation or mRNA expression.

CONCLUSION: Physiological leptin supplementation during lactation contributes to the reversion of changes caused by maternal mild calorie restriction on the liver metabolome. This agrees with a putative role of leptin supplementation preventing or reversing metabolic disturbances caused by gestational metabolic malprogramming. This article is protected by copyright. All rights reserved.