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

• Published in: Molecular nutrition & food research 2021-08, Vol.65 (16), p.e2001046-n/a
• Main Authors: Yau‐Qiu, Zhi Xin, Madrid‐Gambin, Francisco, Brennan, Lorraine, Palou, Andreu, Rodríguez, Ana María
• Format: Article
• Language: English
• Subjects: Animals; Breastfeeding & lactation; Caloric Restriction - adverse effects; calorie restriction; Calories; Deoxyribonucleic acid; Dietary supplements; DNA; DNA Methylation; Energy Intake; Fatty acids; Fatty Acids - analysis; Female; Gene expression; Gestation; Lactation; Leptin; Leptin - administration & dosage; Liver; Liver - metabolism; Male; Maternal Nutritional Physiological Phenomena; metabolic programming; Metabolic response; Metabolism; Metabolites; Metabolome; Metabolomics; NMR; Nuclear magnetic resonance; Nutrient deficiency; Offspring; perinatal nutrition; Phenotypes; Physiological effects; Physiology; Pregnancy; Rats; Rats, Wistar; Reversion
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202001046

Introduction Perinatal nutritional factors can program offspring metabolic phenotype and risk to obesity. This study investigates 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 are performed by NMR and GC‐MS, respectively. Global DNA methylation and the expression by RT‐PCR of key genes involved in different pathways are also determined. By NMR, 15 liver metabolites are 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 shows 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 are 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. Physiological leptin supplementation during lactation contributes to the normalization of liver metabolic phenotype, by reversing, at least partly, alterations in key metabolites associated with maternal mild calorie restriction during gestation. Some of the altered metabolites, reverted by leptin supplementation, are involved in one‐carbon (1C) metabolism, antioxidant defence and carbohydrate, fatty acid, phospholipid, and very long chain fatty acid (VLCFA) metabolism.