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Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans

ABSTRACT: Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans

PROVIDER: PRJNA1013998 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25944677.fastq.gz	Fastqsanger.gz
	SRR25944678.fastq.gz	Fastqsanger.gz
	SRR25944679.fastq.gz	Fastqsanger.gz
	SRR25944680.fastq.gz	Fastqsanger.gz
	SRR25944681.fastq.gz	Fastqsanger.gz

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Long-term intermittent hypoxia in mice induces inflammatory pathways implicated in sleep apnea and steatohepatitis in humans

Project description:Obstructive Sleep Apnea (OSA) engenders repetitive desaturation-reoxygenation sequences called intermittent hypoxia (IH), now widely accepted as an independent risk factor for the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). The specific molecular mechanisms linking IH and the development and progression of NAFLD remain elusive. NAFLD pathogenesis is multifactorial including immune cell-driven inflammation as a key mechanism in the transition from fatty liver to steatohepatitis (NASH). The overall goal of this study was to identify the specific impact of IH on liver inflammation in the absence of major confounders frequently encountered in OSA clinical research (i.e., obesity, diabetes, reduced physical activity). We employed a model of lean mice exposed to long-term IH (16 weeks) and a cohort of lean OSA patients free of comorbidities (n=71) coupled with high-throughput hepatic transcriptomics, lipidomics and targeted serum proteomics. For the first time, we have demonstrated that long-term IH is an independent “hit” sufficient by itself to induce the NASH molecular signatures found in human steatohepatitis transcriptomic datasets.We identified a unique set of biomarkers in mice and humans (PPARs, NRFs, arachidonic acid, IL16, IL20, IFNB and TNFa) associated with early hepatic and systemic inflammation. This molecular connection between IH, sleep apnea and steatohepatitis warrants further investigation in clinical trials and support the systematic implementation of sleep apnea diagnosis in liver disease phenotyping. Our original signatures could allow the identification of potential diagnostic and treatment response markers, as well as therapeutic targets in the comorbid association between NAFLD and OSA.

2024-02-14 | GSE242668 | GEO

Sleep apnea and glucose metabolism

Project description:This study examines the relationship between sleep apnea and glucose metabolism. Physiological studies have demonstrated that 5 days of exposure to intermittent hypoxia (similar to what occurs with sleep apnea) leads to significant improvements in glucose tolerance. Therefore, this study investigates the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action. Keywords: other

2003-07-16 | GSE480 | GEO

Transcription profiling of mice treated with hypoxia and/or sleep fragmentation to investigate the hypothesis that intermittent hypoxia may lead to upregulation of some novel peptide(s) that have a powerful glucose lowering action

2007-12-14 | E-GEOD-480 | biostudies-arrayexpress

Intermittent Hypoxia Induces Cognitive Dysfunction and Hippocampal Gene Expression Changes in a Mouse Model of Obstructive Sleep Apnea

Project description:Obstructive sleep apnea syndrome (OSAS) is characterized by cycles of decreased blood oxygen saturation followed by reoxygenation due to transient apnea. Cognitive dysfunction is a complication of OSAS, but its mechanisms remain unclear. 8-week-old C57BL/6J mice were exposed to intermittent hypoxia (IH) to model OSAS, and cognitive function and hippocampal gene expression were analyzed. Three groups were maintained for 28 days: IH group (oxygen alternating between 10-21% in 2-minute cycles, 8 hours/day), sustained hypoxia group (SH) (10% oxygen, 8 hours/day), and control group (21% oxygen). Behavioral tests and RNA-seq analysis were performed. While Y-maze results showed no differences, the IH group demonstrated impaired memory and learning in passive avoidance tests compared to control and SH groups. RNA-seq revealed specific changes in learning/memory-related genes and oxidative stress response genes in the IH group. RT-qPCR showed decreased Lars2, Hmcn1, and Vstm2l expression in the IH group. Pathway analysis showed the suppression of the KEAP1-NFE2L2 antioxidant pathway in the IH group vs. SH group. Our findings demonstrate that IH may cause cognitive dysfunction through oxidative stress and suppressed antioxidant defenses. IH-specific downregulation of Lars2, Hmcn1, and Vstm2l may contribute to OSAS-related cognitive impairment.

2025-07-25 | GSE299437 | GEO

Epigenome analysis of peripheral blood mononuclear cell (PBMC) samples from obstructive sleep apnea patients and healthy subjects

Project description:Genome wide DNA methylation profiling of obstructive sleep apnea (OSA) patients and healthy subjects. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in peripheral blood mononuclear cell samples. Samples included 8 normal subjects and 16 patients with obstructive sleep apnea syndrome. Bisulphite converted DNA from the 21 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2

2015-12-31 | E-GEOD-61463 | biostudies-arrayexpress

Obstructive sleep apnea is related to alterations in intestinal microbiome and impaired intestinal barrier function

Project description:Objectives: Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. Methods: A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect intestinal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers – intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Results: The severity of OSA was related to differences in the structure and composition of the intestinal microbiome. Enriched Fusobacterium, Megamonasa, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the intestinal microbiome, intestinal barrier biomarkers, and AHI. Conclusions: The study confirms that changes in the intestinal microbiota are related to intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.

2023-08-30 | GSE181270 | GEO

HDL proteome in the sleep apnea syndrome

Project description:We performed proteomics of HDL isolated from patients with sleep apnea syndrome.

2025-11-11 | PXD038190 | JPOST Repository

Intermittent Hypoxia Alters Gene Expression in Peripheral Blood Mononuclear Cells (PBMC) of Healthy Volunteers

Project description:Intermittent hypoxia (IH) of obstructive sleep apnea (OSA) has been implicated in cardiovascular morbidity and mortality1. Although underlying mechanisms of the cardiovascular risk in OSA are not well defined, experiments in cell culture and animal models suggest that IH up-regulates pro-inflammatory genes that can promote atherosclerosis and insulin resistance. We hypothesized that short-term IH (5 h) will induce pro-inflammatory genes in healthy volunteers

2015-07-27 | GSE71356 | GEO

Epigenome analysis of peripheral blood mononuclear cell (PBMC) samples from obstructive sleep apnea patients and healthy subjects

2015-12-31 | GSE61463 | GEO

Methylation analysis of adult patients with severe Obstructive Sleep Apnea before and after CPAP treatment.

Project description:Obstructive Sleep Apnea is a sleep-related breathing disorder. Differential methylation analysis was conducted to evaluate differentially methylated regions across the chromosomes in patients with severe OSA compared to healthy subjects. We further evaluated how these differentially methylated regions were altered with long-term (24 months) continuous positive airway pressure treatment.

2025-12-08 | GSE283783 | GEO

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