Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.
Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.
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腹侧下丘脑OGT驱动脂肪组织脂解和遏制肥胖。
DOI：
10.1126/sciadv.abn8092
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发表时间：
2022-09-02
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
腹内侧下丘脑（VMH）是已知的调节体重和反调节反应。然而，VMH神经元如何调节脂质代谢和能量平衡仍然未知。O-连接的β-d-N-乙酰葡萄糖胺（O-GlcNAc）修饰（O-GlcNAc酰基化）由O-GlcNAc转移酶（OGT）催化，被认为是营养素和激素的细胞传感器。在这里，我们报告，基因消融的OGT在VMH神经元抑制神经元的兴奋性。具有VMH神经元特异性OGT缺失的小鼠显示快速体重增加、肥胖增加和能量消耗减少，而食物摄入或体力活动没有显著变化。肥胖表型与脂肪细胞肥大和白色脂肪组织的脂解减少有关。此外，VMH神经元中的OGT缺失下调交感神经活性并损害白色脂肪组织的交感神经支配。这些研究结果确定OGT在VMH作为一个稳态的设定点，控制体重，并强调了VMH在调节脂质代谢的重要性，通过白色脂肪组织特异性神经支配。VMH通过对白色脂肪组织的神经支配调节脂质代谢，VMH神经元中的OGT具有抗肥胖作用。
The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue–specific innervation. The VMH regulates lipid metabolism through white adipose tissue innervation, and OGT in VMH neurons plays an antiobesogenic role.
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影响因子：
16.2
作者：
Dhillon, H;Zigman, JM;Lowelll, BB
通讯作者：
Lowelll, BB
影响因子：
8.1
作者：
Cheung CC;Krause WC;Edwards RH;Yang CF;Shah NM;Hnasko TS;Ingraham HA
通讯作者：
Ingraham HA
影响因子：
29
作者：
An JJ;Liao GY;Kinney CE;Sahibzada N;Xu B
通讯作者：
Xu B
影响因子：
29
作者：
Jensen-Cody SO;Flippo KH;Claflin KE;Yavuz Y;Sapouckey SA;Walters GC;Usachev YM;Atasoy D;Gillum MP;Potthoff MJ
通讯作者：
Potthoff MJ
影响因子：
5.5
作者：
Gavini, Chaitanya K.;Jones, William C., II;Novak, Colleen M.
通讯作者：
Novak, Colleen M.