Adam C L, Williams P A, Milne J S, Aitken R P, Wallace J M
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
J Neuroendocrinol. 2015 Oct;27(10):765-71. doi: 10.1111/jne.12302.
Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity.
营养对发育中的胎儿下丘脑食欲调节通路产生的不良影响，可能会导致子宫内生长受限、低出生体重后代出现程序性摄食过多和肥胖。在本研究中，首次对妊娠晚期绵羊胎儿（130天；足月为145天）下丘脑主要促食欲和抑食欲基因的表达进行了检测，这些胎儿的母亲在整个孕期处于营养不足（UN）或营养良好（C）状态，或在第90天从营养不足转为营养良好（UN-C）。怀孕是通过将单胎胚胎移植到青春期生长的母羊体内实现的。UN组（n = 9）的体重、胴体脂肪含量和肾周脂肪组织（PAT）质量均低于C组（n = 7），UN-C组胎儿（n = 6）的上述指标处于中间水平，且不受性别的影响。通过逆转录聚合酶链反应检测发现，UN组PAT瘦素基因表达低于C组和UN-C组，且雄性低于雌性。通过与放射性标记的核糖探针进行原位杂交检测基因表达，结果显示，弓状核中神经肽Y（NPY）、刺鼠相关肽（AGRP）和瘦素受体（OBRb）的基因表达在UN组胎儿中高于C组，但促阿片黑素皮质素和可卡因及苯丙胺调节转录物的基因表达在两组间无差异。UN-C组胎儿中NPY和AGRP的基因表达处于中间水平，OBRb的基因表达与C组胎儿无差异。在所有组中，NPY、AGRP和OBRb的基因表达与胎儿胴体脂肪含量以及PAT瘦素基因表达呈负相关。雄性AGRP的mRNA表达高于雌性，NPY和OBRb也呈现类似趋势。因此，孕期全程母体营养不足会增加妊娠晚期胎儿下丘脑促食欲基因的表达，而在妊娠最后三分之一阶段改善母体营养后，表达水平基本恢复正常。这些发现可能对避免或纠正产后摄食过多和肥胖的产前编程具有重要意义。
