The Association of Fetal Malnutrition with Metabolic Syndrome in Adulthood

本研究旨在探讨代谢综合征发生的可能机制。通过母体限食建立了胎儿营养不良(UN子代)的小鼠模型。联合国子孙后代在成年后因高脂饮食、血脂异常、糖耐量受损和血压升高而加速肥胖。在联合国子代中，我们发现了新生儿期瘦素激增的过早发生，这使得下丘脑能量调节中对瘦素的敏感性达到永久性的低水平，并伴随着下丘脑神经回路的结构变化，如神经肽Y(NPY)和可卡因和苯丙胺调节转录本(CART)，导致高脂饮食下肥胖的加速以及糖代谢的受损(尤拉·S，Itoh H等，Cell Metab，2005，1,371)。因此，我们在这里证明，新生儿期过早的瘦素激增在肥胖和相关的有害代谢紊乱的发育起源中起着关键作用。

The purpose of the present study was to investigate a possible mechanism of developmental origins of metabolic syndrome.We developed a mouse animal model of fetal undernutrition (UN offspring) by maternal food restriction. The UN offspring developed an acceleration of obesity on high fat diet, dyslipidemia, impaired glucose tolerance and blood pressure increase in adulthood. In the UN offspring, we reveled a premature onset of leptin surge during neonatal period, which programmed permanent low leptin sensitivity in the hypothalamic energy regulation, concomitant with structural changes of hypothalamic neuronal circuit, such as neuropeptide Y (NPY) and cocaine and amphetamine regulated transcript (CART), contributing to an acceleration of obesity on high fat diet as well as impaired glucose metabolism (Yura S, Itoh H et al., Cell Metab, 2005,1,371).Thus, we here demonstrated that premature leptin surge during neonatal period plays a pivotal role in the developmental origins of obesity and associated detrimental metabolic disorders.