Ladyman S R
Centre for Studies in Behavioural Neurobiology, Concordia University, Montreal, Quebec, Canada.
J Neuroendocrinol. 2008 Feb;20(2):269-77. doi: 10.1111/j.1365-2826.2007.01628.x. Epub 2007 Nov 22.
The adipose-derived hormone leptin primarily acts in the hypothalamus to decrease appetite and increase energy expenditure, thereby maintaining body fat levels around a set point. Pregnancy is a physiological state where this feedback mechanism is not beneficial. Successful reproductive efforts are highly demanding on the resources of the mother; thus, it is imperative that the maternal body can increase energy stores without restraint. Food intake, fat mass and serum leptin concentrations increase during pregnancy in the rat, suggesting that the feedback loop between adipose tissue and appetite is disrupted and a state of leptin resistance exists. In support of this, there is an attenuation of the satiety response to exogenous leptin administration in pregnant rats. This state of leptin resistance is associated with impaired activation of the leptin-induced Janus activating kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the ventromedial nucleus of the hypothalamus (VMH) and arcuate nucleus, and reduced expression of leptin receptor mRNA in the VMH. Furthermore, pregnant rats do not show a satiety response to exogenous alpha-melanocyte stimulating hormone. This model offers the possibility of examining how hypothalamic leptin signalling can be modified in response to changes in physiological conditions.
脂肪源性激素瘦素主要作用于下丘脑，以降低食欲并增加能量消耗，从而将体脂水平维持在设定点左右。怀孕是一种生理状态，在这种状态下这种反馈机制并无益处。成功的生殖过程对母体资源的要求很高；因此，母体能够不受限制地增加能量储备至关重要。在大鼠怀孕期间，食物摄入量、脂肪量和血清瘦素浓度都会增加，这表明脂肪组织与食欲之间的反馈回路被破坏，存在瘦素抵抗状态。支持这一点的是，给怀孕大鼠注射外源性瘦素后，饱腹感反应会减弱。这种瘦素抵抗状态与下丘脑腹内侧核（VMH）和弓状核中瘦素诱导的Janus激活激酶（JAK）/信号转导和转录激活因子（STAT）信号通路的激活受损以及VMH中瘦素受体mRNA表达降低有关。此外，怀孕大鼠对外源性α-黑素细胞刺激素没有饱腹感反应。该模型为研究下丘脑瘦素信号如何响应生理条件变化而被改变提供了可能性。
