Scholarlink

Background <p>Chronic sleep deprivation (SD) from shift work and a high-fat diet (HFD) disrupt circadian rhythms and affect physiological systems, yet their impact on lung circadian rhythms remains poorly understood.</p> Methods <p>This study used a bar-deprivation apparatus to create an SD model with 5&#xa0;days of continuous SD followed by 10&#xa0;days of intermittent SD, repeated five times, alongside an HFD intervention. Forty-six C57BL/6&#xa0;J mice were divided into four groups: control (CON), SD, HFD, and SD_HFD. Assessments included neuromuscular strength, motor coordination, emotional state, cognitive memory, and lung tissue pathology. Transcriptomic and metabolomic analyses were performed on the samples, followed by integrated pathway analysis.</p> Results <p>Behavioral assessments showed notable impairments across the groups. SD mice had poor motor coordination, increased activity in the open-field test, and spatial learning and memory deficits. HFD mice showed reduced motor skills and cognitive function. Interestingly, SD_HFD mice had better muscle strength. Histochemical analysis revealed remarkable lung tissue changes in the SD, HFD, and SD_HFD groups compared with the CON group, with distorted structures, thickened alveolar walls, and increased collagen. Integrated transcriptome–metabolome analysis revealed distinctly enriched pathways among the experimental groups. The SD group showed enrichment in purine metabolism and pyrimidine synthesis, while purine metabolism, amino acid biosynthesis, and arginine/proline metabolism were enriched in the HFD group. The SD_HFD group presented enrichment in purine metabolism, lysine degradation, and steroid hormone biosynthesis. Purine metabolism was a common enriched pathway across all groups. Hypoxanthine, a key molecule, contributes to lung injury via oxidative stress from ROS generation during its conversion to uric acid.</p> Conclusions <p>SD induces manic-like behavioral changes by disrupting circadian rhythms and interacts in a tissue-specific manner with an HFD. Aberrant purine metabolism and related oxidative stress are key mechanisms underlying lung injury.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Multi-omics analysis of the individual and combined effects of long-term sleep deprivation and a high-fat diet on lung injury

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月17日

查看全文
  • Min Zhu,
  • Xuehan Yuan,
  • Zihuan Hu,
  • Yihan Gao,
  • Yuqin Wu,
  • Chang Chen,
  • Peng Duan,
  • Junwen Chen

摘要

Background

Chronic sleep deprivation (SD) from shift work and a high-fat diet (HFD) disrupt circadian rhythms and affect physiological systems, yet their impact on lung circadian rhythms remains poorly understood.

Methods

This study used a bar-deprivation apparatus to create an SD model with 5 days of continuous SD followed by 10 days of intermittent SD, repeated five times, alongside an HFD intervention. Forty-six C57BL/6 J mice were divided into four groups: control (CON), SD, HFD, and SD_HFD. Assessments included neuromuscular strength, motor coordination, emotional state, cognitive memory, and lung tissue pathology. Transcriptomic and metabolomic analyses were performed on the samples, followed by integrated pathway analysis.

Results

Behavioral assessments showed notable impairments across the groups. SD mice had poor motor coordination, increased activity in the open-field test, and spatial learning and memory deficits. HFD mice showed reduced motor skills and cognitive function. Interestingly, SD_HFD mice had better muscle strength. Histochemical analysis revealed remarkable lung tissue changes in the SD, HFD, and SD_HFD groups compared with the CON group, with distorted structures, thickened alveolar walls, and increased collagen. Integrated transcriptome–metabolome analysis revealed distinctly enriched pathways among the experimental groups. The SD group showed enrichment in purine metabolism and pyrimidine synthesis, while purine metabolism, amino acid biosynthesis, and arginine/proline metabolism were enriched in the HFD group. The SD_HFD group presented enrichment in purine metabolism, lysine degradation, and steroid hormone biosynthesis. Purine metabolism was a common enriched pathway across all groups. Hypoxanthine, a key molecule, contributes to lung injury via oxidative stress from ROS generation during its conversion to uric acid.

Conclusions

SD induces manic-like behavioral changes by disrupting circadian rhythms and interacts in a tissue-specific manner with an HFD. Aberrant purine metabolism and related oxidative stress are key mechanisms underlying lung injury.