Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling or Leptin Resistance in Obesity.
Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling or Leptin Resistance in Obesity.
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DOI：
10.3389/fendo.2015.00119
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发表时间：
2015
影响因子：
5.2
通讯作者：
Rohner-Jeanrenaud F
中科院分区：
文献类型：
--
作者：
Altirriba J;Poher AL;Rohner-Jeanrenaud F
本文综述了催产素在不同动物模型和人类中治疗肥胖的作用，重点介绍了对食物摄入量的中枢控制，催产素对脂肪组织的影响，以及催产素和瘦素之间的关系。催产素是一种下丘脑的非肽，主要在脑室旁和视上核中合成，投射到垂体，在那里到达外周循环，以及其他大脑区域。此外，瘦素调节催产素水平并激活下丘脑室旁核中的催产素神经元，而下丘脑室旁核支配孤束核，这是脑源性催产素效应的部分原因。考虑到催产素位于瘦素的下游，推测催产素治疗对瘦素抵抗的DIO动物以及瘦素或瘦素受体缺陷者的体重减轻是有效的。几个小组已经证明，在这样的动物模型(大鼠、小鼠和恒河猴)中，中枢或外周给予催产素会减少体重，这主要是由于脂肪质量的减少，证明了催产素治疗能够部分克服瘦素缺乏或抵抗。此外，一项初步的临床研究证明了催产素在治疗人类肥胖症方面的有效性，证实了在不同动物模型中获得的结果。现在需要进行更大规模的多中心研究，以确定催产素治疗的有益效果是否不仅适用于肥胖者，也适用于2型糖尿病患者。这些研究还应该对人类催产素作用的分子机制有所了解。
This review summarizes the existing literature on the effects of oxytocin administration in the treatment of obesity in different animal models and in humans, focusing on the central control of food intake, the oxytocin effects on adipose tissue, and the relationships between oxytocin and leptin. Oxytocin is a hypothalamic nonapeptide synthesized mainly in the paraventricular and supraoptic nuclei projecting to the pituitary, where it reaches the peripheral circulation, as well as to other brain regions. Moreover, leptin modulates oxytocin levels and activates oxytocin neurons in the hypothalamic paraventricular nucleus, which innervates the nucleus of the solitary tract, partly responsible for the brain-elicited oxytocin effects. Taking into account that oxytocin is located downstream leptin, it was hypothesized that oxytocin treatment would be effective in decreasing body weight in leptin-resistant DIO animals, as well as in those with leptin or with leptin receptor deficiency. Several groups have demonstrated that in such animal models (rats, mice, and rhesus monkeys), central or peripheral oxytocin administration decreases body weight, mainly due to a decrease in fat mass, demonstrating that an oxytocin treatment is able to partly overcome leptin deficiency or resistance. Moreover, a pilot clinical study demonstrated the efficiency of oxytocin in the treatment of obesity in human subjects, confirming the results obtained in the different animal models. Larger multicenter studies are now needed to determine whether the beneficial effects of oxytocin treatment can apply not only to obese but also to type 2 diabetic patients. These studies should also shed some light on the molecular mechanisms of oxytocin action in humans.