Fto-modulated lipid niche regulates adult neurogenesis through modulating adenosine metabolism
Fto-modulated lipid niche regulates adult neurogenesis through modulating adenosine metabolism
复制标题
Fto 调节的脂质生态位通过调节腺苷代谢来调节成人神经发生
DOI：
10.1093/hmg/ddaa171
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发表时间：
2020-08-15
影响因子：
3.5
通讯作者：
Li, Xuekun
中科院分区：
文献类型：
--
作者：
Gao, Hui;Cheng, Xuejun;Li, Xuekun
成体神经发生受多种因素的调控，包括局部环境，即神经源性生态位。然而，大脑中的脂质是否调节成人神经发生和相关机制在很大程度上仍不清楚。在目前的研究中，我们发现在出生后神经元发育过程中，脂质在大脑中积累。在脂质中条件性敲除FTO(CKO)不仅降低了脑组织中的脂质水平，而且还损害了小鼠的学习记忆能力。此外，脂质中FTO缺乏不影响成体神经干细胞(ANSCs)的增殖，但通过诱导细胞凋亡来抑制成体神经发生。从机制上讲，脂类中FTO的特异性缺失改变了脂肪细胞的基因表达，增加了腺苷的分泌。腺苷治疗可促进新生神经元的凋亡。总体而言，这些结果揭示了脂质生态位及其相关机制在调节成人神经发生中的重要作用。
Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.