Role of premature leptin surge in obesity resulting from intrauterine undernutrition
Role of premature leptin surge in obesity resulting from intrauterine undernutrition
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DOI：
10.1016/j.cmet.2005.05.005
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发表时间：
2005-06-01
期刊：
影响因子：
29
通讯作者：
Fujii, S
中科院分区：
文献类型：
--
作者：
Yura, S;Itoh, H;Fujii, S
宫内营养不良与肥胖密切相关，后者与成年后的有害代谢后遗症有关。我们报告了一个小鼠模型，在该模型中，胎儿营养不良的后代(UN后代)，当喂食高脂饮食(HFD)时，出现明显的体重增加和肥胖。在新生儿期，与宫内营养正常的子代(NN子代)相比，UN子代的新生儿瘦素高峰出现的时间较早。出乎意料的是，由外源性瘦素注射在神经网络后代中产生的过早的瘦素激增导致了HFD体重增加的加速。联合国子代和新生儿瘦素治疗的NN子代对常规饮食(RCD)的急性外周瘦素注射反应受损，瘦素到大脑的运输受损，下丘脑神经末梢密度增加。目前的研究表明，过早的瘦素激增改变了下丘脑的能量调节，并有助于“健康和疾病的发育起源”。
Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."