醋酸盐能在睡眠中断时促进新陈代谢,提高认知能力。

Cell metabolism Pub Date : 2024-09-03 Epub Date: 2024-08-19 DOI:10.1016/j.cmet.2024.07.019
Qinqin He, Liwei Ji, Yanyan Wang, Yarong Zhang, Haiyan Wang, Junyan Wang, Qing Zhu, Maodi Xie, Wei Ou, Jun Liu, Kuo Tang, Kening Lu, Qingmei Liu, Jian Zhou, Rui Zhao, Xintian Cai, Nanfang Li, Yang Cao, Tao Li
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引用次数: 0

摘要

睡眠对整体健康至关重要,睡眠中断与代谢、认知和心血管功能障碍的风险增加有关;然而,人们对其分子机制仍然知之甚少。本研究利用慢性睡眠片段(SF)小鼠模型研究了睡眠紊乱如何导致代谢失衡和认知功能障碍。与对照组相比,SF 小鼠的认知能力、糖代谢和胰岛素敏感性均受损。我们发现下丘脑星形胶质细胞中乙酸盐含量的增加是 SF 小鼠的一种防御反应。通过注入醋酸盐或删除星形胶质细胞特异性 Acss1 来提高醋酸盐水平,我们观察到 SF 小鼠的代谢和认知障碍得到了缓解。从机理上讲,乙酸盐能结合并激活丙酮酸羧化酶,从而恢复糖酵解和三羧酸循环。在最常受 SF 影响的人群中,阻塞性睡眠呼吸暂停患者在合并 2 型糖尿病时表现出乙酸盐水平升高。我们的研究揭示了醋酸盐对睡眠引起的代谢和认知障碍的保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Acetate enables metabolic fitness and cognitive performance during sleep disruption.

Acetate enables metabolic fitness and cognitive performance during sleep disruption.

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments.

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