Taking a population perspective on child health
Taking a population perspective on child health
复制标题
DOI：
10.1136/adc.83.1.7
复制
发表时间：
2000-07-01
影响因子：
5.2
通讯作者：
Blair, M
中科院分区：
文献类型：
--
作者：
Blair, M
我们对脂肪代谢和生殖轴之间潜在遗传联系的认识可以追溯到20世纪50年代，当时肥胖（ob/ob）小鼠品系首次被描述。这些小鼠不仅明显贪食，并迅速发展肥胖与高血糖症和胰岛素抵抗，但他们也不育。1直到1994年，瘦素（ob）基因被定位克隆，并在ob/ob小鼠的小鼠瘦素编码序列中发现了突变，才认识到肥胖的原因。2.肥胖基因型小鼠的表型表明，瘦素主要表达于脂肪细胞，具有抑制食欲和刺激能量消耗的作用。人们很快就发现，瘦素也会影响生殖系统。重组瘦素可逆转雄性和雌性ob/ob小鼠的不育。在人类中，最初的研究集中在瘦素在肥胖中可能发挥的作用。瘦素缺乏可能导致普通人类肥胖的假设很快就被否定了。血清瘦素浓度与体重指数或体脂百分比之间存在指数关系，5这意味着，随着一个人变得越来越胖，对瘦素的厌食作用也变得不敏感。然而，人体脂肪和生殖能力之间的关系早已被认识到。神经性厌食症和剧烈的体育锻炼都与促性腺激素水平降低有关，而Frisch提出，必须积累一定量的身体脂肪才能实现月经规律。[7]因此，外周能量储存（脂肪）与身体发育和生殖能力的中枢调节之间存在着明显的联系。在过去的四年里，对动物和人类的研究提供了令人信服的证据，证明瘦素可能是一种神经体液介质，能够在营养摄入和体脂储存的程度之间向中枢神经系统发出信号。瘦素和下丘脑-垂体-性腺功能之间的联系的检查主要在小鼠模型中进行。在高等物种中，这种关系不太明确。此外，当促性腺激素释放激素（GnRH）脉冲发生器被重新激活时，瘦素在青春期开始时可能发挥的作用尚未阐明。本文将回顾小鼠、大鼠、猴和人的数据，并讨论可能涉及的神经网络。
Our knowledge of the potential genetic link between fat metabolism and the reproductive axis dates back to the 1950s when the obese (ob/ob) mouse strain was first described. These mice were not only distinctly hyperphagic and rapidly developed obesity associated with hyperglycaemia and insulin resistance, but they were also infertile. 1 It was not until 1994 when the leptin (ob) gene was postionally cloned and a mutation was identified in the coding sequence of murine leptin in ob/ob mice that the cause of their obesity was recognised. 2 As predicted from the phenotype of ob/ob mice, leptin, which is principally expressed in adipocytes, had potent actions to suppress appetite and stimulate energy expenditure. It rapidly became clear that leptin could also influence the reproductive system. The sterility of male and female ob/ob mice could be reversed when recombinant leptin was administered. 3 4In humans, initial studies focused on the possible role that leptin may play in obesity. The hypothesis that leptin deficiency may contribute to common human obesity was soon rejected. An exponential relation between serum leptin concentration and body mass index or percentage body fat was described, 5 implying that, as a person became fatter, so insensitivity to the anorexigenic action of leptin developed. However, the relation between body fat and reproductive ability in humans has long been recognised. Both anorexia nervosa and intense physical training are associated with reduced gonadotrophin levels, 6 while Frisch had proposed that a certain amount of body fat must be accrued to achieve regular menstruation. 7 There is therefore a clear link between peripheral energy stores (in fat) and central regulation of physical development and reproductive capacity. Studies in animals and humans over the last four years have provided compelling evidence that leptin may be a neurohumoral mediator capable of signalling between the extent of nutritional intake and body fat store to the central nervous system. Examination of the link between leptin and hypothalamic-pituitary-gonadal function has been undertaken mainly in the murine model. The relation in higher species is less well defined. In addition, the role that leptin may play in the onset of puberty, when the gonadotrophin releasing hormone (GnRH) pulse generator is being re-activated, has not been clarified. A review of data from the mouse, rat, monkey, and man and discussion of the possible neural networks involved will be presented.