Sympathetic blockage attenuates fasting-induced hepatic steatosis
Sympathetic blockage attenuates fasting-induced hepatic steatosis
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交感神经阻滞可减轻禁食引起的肝脂肪变性
DOI：
10.1097/wnr.0000000000001844
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发表时间：
2022-12-14
期刊：
影响因子：
1.7
通讯作者：
Li，Guolin
中科院分区：
文献类型：
--
作者：
Zheng，Lin;Gong，Lijun;Li，Guolin
虽然中枢神经系统协调全身代谢，但肝脂肪变性的神经机制仍不清楚。本研究旨在探讨禁食诱导肝脂肪变性的神经机制。在禁食前用6-羟基多巴胺预处理小鼠以阻断交感神经活动，并探索化学交感神经切除术对禁食诱导的肝脏脂肪变性和转录变化的潜在影响。禁食24小时导致明显的肝脏脂肪变性，低核心温度，以及与冷诱导的白色脂肪分解相似的作用。肝脏mRNA表达的改变表明，肝脏脂质蓄积不是由于肝脏脂肪生成增加或脂肪酸氧化减少，而是由于CD 36上调所示的脂肪酸摄取增加。通过化学交感神经切除术阻断交感神经系统可减弱禁食诱导的肝脂肪变性，并抑制肝脏中CD 36的上调，但并没有明显改变与脂肪生成或脂肪酸氧化相关的基因表达。这些发现表明交感神经系统通过调节CD 36表达和脂肪向肝脏的运输来协调禁食诱导的肝脏脂肪变性的机制，这为揭示脂肪肝疾病的新靶点提供了线索。
Although the central nervous system coordinates whole-body metabolism, the neural mechanism for hepatic steatosis remains unclear. This study is aimed to explore the neural mechanism of fasting-induced hepatic steatosis. Mice were pretreated with 6-hydroxydopamine to block sympathetic nerve activity before fasting, and to explore the potential effects of chemical sympathectomy on fasting-induced hepatic steatosis and transcriptional changes. Twenty-four hours fasting led to obvious hepatic steatosis, low-core temperature, and similar effects to cold-induced white adipose lipolysis. The alterations in hepatic mRNA expression revealed that the hepatic lipid accumulation did not result from an increase in hepatic lipogenesis or a decrease in fatty acid oxidation but from enhanced fatty acid uptake as indicated by upregulation of CD36. Blockage of the sympathetic nervous system via chemical sympathectomy attenuated fasting-induced hepatic steatosis and suppressed CD36 upregulation in the liver, but did not obviously alter the expression of genes associated with lipogenesis or fatty acid oxidation. These findings indicate that the sympathetic nervous system orchestrates the mechanism for fasting-induced hepatic steatosis via modulating CD36 expression and adipose fat trafficking into the liver, which provides clues to reveal new targets for fatty liver diseases.