Szostaczuk Nara, Sánchez Juana, Konieczna Jadwiga, Palou Andreu, Picó Catalina
Laboratory of Molecular Biology, Nutrition and Biotechnology (Nutrigenomics and Obesity), University of the Balearic Islands, Palma, Spain.
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Palma, Spain.
Front Physiol. 2018 Mar 21;9:256. doi: 10.3389/fphys.2018.00256. eCollection 2018.
Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction. Three groups of male rats were studied at a juvenile age (25 days old) and during adulthood (3 and 6 months old): the offspring of fed dams (controls), the offspring of dams that were diet restricted (20%) from days 1 to 12 of gestation (CR), and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk) throughout lactation (CR-Leptin). The density of TyrOH-immunoreactive (TyrOH) fibers and the levels of Tyrosine hydroxylase (TyrOH)-used as potential markers of functional sympathetic innervation-were measured in stomach. Plasma leptin and ghrelin levels were also determined. Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH fibers (-46%) and TyrOH levels (-47%) in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%), and a lower leptin/ghrelin ratio (-28 and -37% at 3 and 6 months, respectively). Leptin intake during lactation is able to reverse the alterations in the density of TyrOH fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an essential nutrient during lactation.
研究表明，大鼠孕期营养不足会降低后代外周组织（包括胃）中交感神经支配标志物的表达。这与胃分泌减少和胃饥饿素循环水平降低有关。鉴于哺乳期摄入瘦素在预防肥胖和逆转不良发育编程效应方面的关键作用，我们旨在探究补充瘦素是否可以逆转轻度孕期热量限制所引起的上述改变。我们研究了三组雄性大鼠，分别在幼年（25日龄）和成年期（3个月和6个月龄）进行观察：喂食正常母鼠的后代（对照组）、孕期第1天至第12天饮食受限（20%）的母鼠后代（CR组），以及在整个哺乳期每天口服一剂瘦素（相当于它们从母乳中每天所能获得平均量的5倍）的CR组大鼠（CR-瘦素组）。我们测量了胃中酪氨酸羟化酶免疫反应性（TyrOH）纤维的密度以及酪氨酸羟化酶（TyrOH）的水平，将其作为功能性交感神经支配的潜在标志物。同时还测定了血浆瘦素和胃饥饿素水平。与对照组相比，25日龄的CR组大鼠胃中TyrOH纤维密度（-46%）和TyrOH水平（-47%）较低，但CR-瘦素组大鼠未出现这种情况。CR组动物的这些改变在6个月龄时有所缓解，差异不再显著。成年CR-瘦素组动物的血浆胃饥饿素水平高于CR组动物，尤其是在3个月龄时（+16%），且瘦素/胃饥饿素比值较低（3个月和6个月龄时分别为-28%和-37%）。哺乳期摄入瘦素能够逆转大鼠胃中TyrOH纤维密度的改变，并使与轻度孕期热量限制相关的升高的瘦素/胃饥饿素比值恢复正常，这支持了瘦素作为哺乳期必需营养素的重要性。
