Kisspeptin, encoded by Kiss1 gene expressing neurons in the hypothalamus, is a requisite for fertility and now appears critical in the regulation of energy balance. Kisspeptin neurons, particularly those in the arcuate nucleus (ARC), receive information directly and indirectly from a diverse array of brain regions including the bed nucleus of the stria terminalis, amygdala, interpeduncular nucleus, hippocampus, and cortex. On the other hand, kisspeptin neuron projections clearly extend to GnRH neuron cell bodies in rodents, sheep, and primates and beyond to other—non-GnRH—brain areas. Kiss1r, the kisspeptin receptor, is expressed on GnRH neurons and also in additional brain areas and peripheral tissues, indicating a nonreproductive role. Kisspeptin neurons clearly receive signals pertinent to deviations in energy balance but are now recognized as a novel neuroendocrine player in the fine balance of energy intake and expenditure. Mice that have a dysfunctional gene for Kiss1r develop an obese and diabetic phenotype. The mechanism behind this altered metabolic state is still mostly unknown; however, Kiss1r expression in the pancreas and brown adipose tissue is clearly functional and required for normal glucose tolerance and energy expenditure, respectively. Kisspeptin neurons in the ARC also participate in the generation of circadian rhythms, specifically those concerning food intake and metabolism, offering a potential explanation for the obesity in Kiss1r knockout mice. Overall, the discoveries of new mechanistic roles for kisspeptin in both normal and pathophysiologic states of energy balance may lead to further understating of obesity prevalence and novel therapeutic targets and interventions.

Kisspeptin，由Kiss1编码下丘脑中表达神经元的基因是生育的必要条件，现在在能量平衡的调节中显得至关重要。Kisspeptin 神经元，尤其是弓状核 (ARC) 中的神经元，直接或间接地从包括终纹床核、杏仁核、脚间核、海马和皮层在内的各种大脑区域接收信息。另一方面，kisspeptin 神经元投射显然延伸到啮齿动物、绵羊和灵长类动物的 GnRH 神经元细胞体，并延伸到其他非 GnRH 大脑区域。Kiss1r，kisspeptin 受体，在 GnRH 神经元以及其他大脑区域和外周组织中表达，表明其具有非生殖作用。Kisspeptin 神经元清楚地接收与能量平衡偏差相关的信号，但现在被认为是能量摄入和消耗的精细平衡中的新型神经内分泌参与者。Kiss1r 基因功能失调的小鼠会出现肥胖和糖尿病表型。这种改变的代谢状态背后的机制仍然是未知的。然而，胰腺和棕色脂肪组织中的 Kiss1r 表达显然是功能性的，并且分别是正常葡萄糖耐量和能量消耗所必需的。ARC 中的 Kisspeptin 神经元也参与昼夜节律的产生，特别是与食物摄入和代谢有关的节律，为 Kiss1r 基因敲除小鼠的肥胖提供了潜在的解释。全面的，