Yau-Qiu Zhi Xin, Madrid-Gambin Francisco, Brennan Lorraine, Palou Andreu, Rodríguez Ana María
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics and obesity), University of the Balearic Islands (UIB), Palma de Mallorca, Spain.
Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain.
Mol Nutr Food Res. 2021 Aug;65(16):e2001046. doi: 10.1002/mnfr.202001046. Epub 2021 Aug 2.
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.
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.
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.
围产期营养因素可设定后代的代谢表型和肥胖风险。本研究调查了（哺乳期）补充瘦素在改善孕期母体轻度热量限制对幼鼠后代肝脏代谢反应造成的不良编程影响方面的潜在作用。
分别通过核磁共振（NMR）和气相色谱 - 质谱联用（GC - MS）对肝脏样本进行非靶向和靶向代谢组学研究。还测定了全基因组DNA甲基化以及参与不同途径的关键基因的逆转录聚合酶链反应（RT - PCR）表达。通过核磁共振观察到，在出生后第25 - 27天，孕期热量限制母鼠的后代（CR组）中有15种肝脏代谢物发生了改变。哺乳期补充生理剂量的瘦素可部分逆转CR条件对这些代谢物中大多数的影响。此外，通过气相色谱 - 质谱联用进行的靶向脂肪酸分析表明，CR后代肝脏中某些极长链脂肪酸（VLCFA）的浓度显著降低，补充瘦素可部分或完全逆转这种情况。在全基因组DNA甲基化或mRNA表达方面未发现显著变化。
哺乳期补充生理剂量的瘦素有助于逆转母体轻度热量限制对肝脏代谢组造成的变化。这与补充瘦素在预防或逆转孕期代谢不良编程引起的代谢紊乱方面的假定作用相符。
