Epidemiological and genome-wide association studies (GWAS) have shown high correlation between childhood obesity and advance in puberty. Early age at menarche is associated with a series of morbidities, including breast cancer, cardiovascular diseases, type 2 diabetes, and obesity. The adipocyte hormone leptin signals the amount of fat stores to the neuroendocrine reproductive axis via direct actions in the brain. Using mouse genetics, we and others have identified the hypothalamic ventral premammillary nucleus (PMv) and the agouti-related protein (AgRP) neurons in the arcuate nucleus (Arc) as primary targets of leptin action in pubertal maturation. However, the molecular mechanisms underlying leptin's effects remain unknown. Here we assessed changes in the PMv and Arc transcriptional program during leptin-stimulated and typical pubertal development using overlapping analysis of bulk RNA sequecing, TRAP sequencing, and the published database. Our findings demonstrate that dynamic somatodendritic remodeling and extracellular space organization underlie leptin-induced and typical pubertal maturation in female mice.

流行病学和全基因组关联研究（GWAS）显示，儿童肥胖与青春期进展之间存在高度相关性。初潮初潮与一系列疾病有关，包括乳腺癌，心血管疾病，2型糖尿病和肥胖症。脂肪细胞激素瘦素通过大脑中的直接作用向神经内分泌生殖轴发出脂肪储存量的信号。利用小鼠遗传学，我们和其他人已经确定了弓状核（Arc）中下丘脑腹侧前乳突核（PMv）和刺骨相关蛋白（AgRP）神经元是瘦素在青春期成熟中的主要作用靶点。然而，瘦蛋白作用的潜在分子机制仍然未知。在这里，我们使用大量RNA测序，TRAP测序和已发布数据库的重叠分析，评估了瘦素刺激的和典型的青春期发育过程中PMv和Arc转录程序的变化。我们的发现表明，动态体细胞树突重塑和细胞外空间组织是瘦素诱导的雌性小鼠典型青春期的基础。