期刊文献

Distinct Hepatic Metabolic Reprogramming in Acute and Chronic Sleep Deprivation and the Protective Effects of the Chalcone Analogue TAK 收藏

在急性和慢性睡眠剥夺中独特的肝代谢重编程以及Chalcone Abalogue TAK的保护作用
原文求助 发布源
作者
Yifang Wang (https://orcid.org/0000-0003-2040-6078) [1];Yachong Hu (https://orcid.org/0009-0001-2495-8200) [2];Pengxiao Wang [3];Ranrui Hu [4];Zhongqi Chen (https://orcid.org/0009-0002-8579-6070) [5];Tiantian Zhang [6];Jiankang Liu (https://orcid.org/0000-0003-1207-5037) [7];Mami Noda (https://orcid.org/0000-0002-9674-069X) [8];Jiangang Long (https://orcid.org/0000-0001-8074-957X) [9];Yunhua Peng (https://orcid.org/0000-0001-8814-2801) [10];
作者单位
[1]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [2]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [3]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [4]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [5]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [6]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [7]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [8]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [9]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; [10]Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China;
发布日期
2025-4-8
页码
3485
DOI
10.3390/ijms26083485
来源信息
International Journal of Molecular Sciences ISSN：1422-0067, 2025年, 26卷, 8期, 3485页
摘要
The prevalence of sleep deprivation is increasing worldwide. Despite the vital roles that the liver plays in metabolism and immune response, hepatic dysfunctions in acute sleep deprivation (ASD) and chronic sleep deprivation (CSD) remain underexplored. Additionally, the effects of the newly developed chalcone analog, 1-(2,3,4-trimethoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-acrylketone (TAK), were evaluated as a potential therapeutic chemical for mitigating SD-induced hepatic damage. A modified multi-platform method was employed to prepare animal models of 72 h ASD and 21-day CSD in rats. TAK (50 mg/kg/day) was administered through irrigation starting one week before the experiment and continuing until the end. ASD triggered hepatic lipid accumulation and inflammation, whereas CSD resulted in pathological portal area expansion and fibrosis, with comparatively fewer disturbances in liver metabolism and inflammation. TAK effectively alleviated ASD-induced disruptions in glycogen synthesis via PI3K/AKT/GSK3/GYS2 pathways, abnormal lipid accumulation via SREBP1/FASN/ACC, liver inflammation by balancing M1 and M2 macrophages, and liver fibrosis induced by ASD/CSD. This study provides valuable insights into the different mechanisms of liver damage induced by severe ASD and mild CSD. Additionally, TAK has been proposed as a potential therapeutic strategy for ultimate SD-related hepatic complications.
摘要译文
在全球范围内，睡眠不足的流行率正在增加。尽管肝脏在代谢和免疫反应中起着至关重要的作用，但急性睡眠剥夺（ASD）和慢性睡眠剥夺（CSD）的肝功能障碍仍未得到充实。此外，将新开发的Chalcone类似物（1-（2,3,4-三甲氧基））-2-（3,4,5-三甲基氧苯基） - 丙烯酮（TAK）评估为潜在的治疗性化学性质，用于减轻SD诱导的SD诱导的hepatic损伤。采用了一种改良的多平台方法，以准备大鼠72小时ASD和21天CSD的动物模型。TAK（50 mg/kg/day）是通过实验开始前一周开始灌溉进行管理的，一直持续到结束。ASD触发了肝脂质的积累和炎症，而CSD导致病理门户区域扩张和纤维化，肝脏代谢和炎症的疾病相对较少。TAK通过PI3K/AKT/GSK3/GYS2途径有效地缓解了ASD诱导的糖原合成中的破坏，通过SREBP1/FASN/ACC的脂质累积异常，通过平衡M1和M2巨噬细胞和ASD/CSD引起的Liver纤维化，通过平衡M1和M2巨噬细胞来平衡肝脏炎症。这项研究为严重的ASD和轻度CSD引起的肝损害的不同机制提供了宝贵的见解。此外，提议TA为最终SD相关肝并发症的潜在治疗策略。
Yifang Wang (https://orcid.org/0000-0003-2040-6078) [1];Yachong Hu (https://orcid.org/0009-0001-2495-8200) [2];Pengxiao Wang [3];Ranrui Hu [4];Zhongqi Chen (https://orcid.org/0009-0002-8579-6070) [5];Tiantian Zhang [6];Jiankang Liu (https://orcid.org/0000-0003-1207-5037) [7];Mami Noda (https://orcid.org/0000-0002-9674-069X) [8];Jiangang Long (https://orcid.org/0000-0001-8074-957X) [9];Yunhua Peng (https://orcid.org/0000-0001-8814-2801) [10];. Distinct Hepatic Metabolic Reprogramming in Acute and Chronic Sleep Deprivation and the Protective Effects of the Chalcone Analogue TAK[J]. International Journal of Molecular Sciences, 2025,26(8): 3485