Han Xingfa, Burger Laura L, Garcia-Galiano David, Sim Seokmin, Allen Susan J, Olson David P, Myers Martin G, Elias Carol F
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Isotope Research Lab, Sichuan Agricultural University, Ya'an 625014, China.
iScience. 2020 Sep 16;23(10):101563. doi: 10.1016/j.isci.2020.101563. eCollection 2020 Oct 23.
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）表明，儿童肥胖与青春期提前之间存在高度相关性。初潮年龄过早与一系列疾病有关，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在大脑中的直接作用，向神经内分泌生殖轴传递脂肪储存量的信号。利用小鼠遗传学，我们和其他研究人员已确定下丘脑腹侧乳头前核（PMv）和弓状核（Arc）中的刺鼠相关蛋白（AgRP）神经元是瘦素在青春期成熟过程中发挥作用的主要靶点。然而，瘦素作用的分子机制仍然未知。在这里，我们使用批量RNA测序、TRAP测序的重叠分析以及已发表的数据库，评估了在瘦素刺激和典型青春期发育过程中PMv和Arc转录程序的变化。我们的研究结果表明，动态的树突-体细胞重塑和细胞外空间组织是瘦素诱导的以及雌性小鼠典型青春期成熟的基础。
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