能量代谢与生殖关系密切，下丘脑弓状核（ARC）是体内能量代谢和生殖调控的中枢部位，ARC的kisspeptin神经元是调控生殖的分子阀门，我们前期研究发现代谢因子脂联素能调节kisspeptin影响生殖，最近报道kisspeptin也能调节代谢，但kisspeptin调节中枢食欲和能量代谢的机制仍在探索，表观遗传调控机制是调控能量代谢的重要机制，本研究拟从乙酰化和DNA甲基化入手观察kisspeptin对食欲因子POMC和AgRP/NPY基因转录的表观遗传调控机制，然后用化学遗传学方法特异性激活Kiss1-Cre小鼠ARC的kisspeptin神经元，观察其食欲的变化及其表观遗传机制，并用POMC和AgRP神经元特异性敲除kisspeptin受体的小鼠，观察kisspeptin对其食欲的影响及其表观遗传机制。这对防治生殖异常相关的代谢病寻找新的治疗靶点具有重要意义。

It is a close relationship between energy metabolism and reproduction. The arcuate nucleus(ARC) in the hypothalamus is the central part in control of energy metabolism and reproduction. Kisspeptin neuron in the ARC is the molecular regulator of reproduction. Our previous research found that adiponectin, a metabolic factor, can effect on reproduction by regulating kisspeptin. A few more recent reports showed that kisspeptin can also modulate metabolism. However, the mechanism of kisspeptin acts on central appetite and energy metabolism remains unclear. The epigenetic regulation mechanism may be one of the possible mechanisms. This study aims to observe epigenetic mechanism of regulation of kisspeptin on the transcription of POMC and AgRP/NPY that are believed as central appetite factors by acetylation and DNA methylation. Kisspeptin neurons of Kiss1-Cre mice will be specifically activated by chemogenetic method, and the change of appetite and its epigenetic mechanism will be observed. Further, the effects of kisspeptin on its appetite and its epigenetic mechanism will be observed in mice with conditional knockout of kisspeptin receptor in POMC and AgRP neurons. This study will play a critical role in the prevention and exploration new treatments for the metabolic diseases associated with reproductive disorder.