Glutamatergic melanocortin-4 receptor neurons regulate body weight

文献类型： 外文期刊

第一作者： Liu, Haodong

作者： Liu, Haodong;Li, Penghui;Li, Jiacheng;Fan, Qi;Wang, Xing;Du, Chenguang;Liu, Haodong;Li, Penghui;Hai, Rihan;Li, Jiacheng;Fan, Qi;Wang, Xing;Gao, Ruifeng;Du, Chenguang;Li, Xiaojing;Hai, Rihan;Chen, Yujie;Cao, Xiaojuan;Zhang, Xiaoyu;Du, Chenguang;Wang, Kun;Wang, Kun

作者机构：

关键词： body weight; glutamate; locus coeruleus; Melanocortin-4 receptor; melanocortin; neurons; paraventricular hypothalamic nucleus; RRID:007914; RRID: 016963

期刊名称：FASEB JOURNAL （ 影响因子：4.8； 五年影响因子：5.2 ）

ISSN： 0892-6638

年卷期： 2023 年 37 卷 5 期

页码：

收录情况： SCI

摘要： The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVNVGlut2::MC4R and LCVGlut2::MC4R regulation of body weight, and axonal projections of LCVGlut2 neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LCVGlut2 circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LCVGlut2 neurons. The PVN ?LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.

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