Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.
Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.
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DOI：
10.1111/1440-1681.12545
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发表时间：
2016-04
影响因子：
2.9
通讯作者：
D'mello AP
中科院分区：
文献类型：
--
作者：
Qasem RJ;Li J;Tang HM;Pontiggia L;D'mello AP
围产期营养对后代生理的影响主要是在年轻的成年动物中进行的。衰老是代谢灵活性逐渐丧失和疾病发展的一个危险因素。很少有研究检查是否由围产期营养编程的表型持续老化的后代。有害表型的持续存在及其累积代谢效应对于疾病的因果关系很重要。本研究确定了母亲在怀孕和哺乳期间限制蛋白质摄入对1岁雄性后代的摄食量、中枢瘦素敏感性、骨骼健康和对高脂饮食诱导的肥胖症的易感性的影响。Sprague-Dawley大鼠在整个妊娠期和哺乳期接受对照或蛋白质限制饮食，幼仔断奶后进食实验室食物。一岁的低蛋白（LP）的后代表现出摄食过度。腹膜内（i. p.）注射瘦素减少摄食表明，摄食过多是由中枢瘦素敏感性降低介导的。摄食过多伴随着较低的体重，这表明LP后代的能量消耗增加。瘦素通过交感神经系统（SNS）起作用，对骨密度和骨矿物质含量进行负性调节，LP后代的骨密度和骨矿物质含量降低。LP后代没有表现出对高脂饮食诱导的代谢效应或肥胖的易感性增加。这里提出的结果表明，围产期蛋白质限制的编程效果介导的特定减少中枢瘦素信号转导的途径参与调节食物摄入量沿着与可能增强不同的中枢瘦素信号转导途径通过SNS调节骨量和能量消耗。
The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure.