Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

Area of Science:

• Metabolomics
• Genomics
• Sleep Medicine

Background:

• Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia (IH).
• IH is linked to metabolic dysfunction, including inflammation and insulin resistance in visceral white adipose tissue (vWAT).
• The specific cell types and transcriptional pathways driving these vWAT changes in OSA remain unclear.

Purpose of the Study:

• To investigate the cellular heterogeneity and transcriptional responses within vWAT following IH exposure mimicking OSA.
• To identify cell-specific molecular pathways contributing to IH-induced metabolic dysfunction.

Main Methods:

• Mice were exposed to IH or room air (RA) for 6 weeks.
• Single nucleus RNA sequencing (snRNA-seq) was performed on vWAT.
• Differential gene expression (DEGs), gene ontology, and pathway analyses were conducted across identified cell types.

Main Results:

• IH induced significant transcriptional alterations across 14 distinct vWAT cell types compared to RA.
• Cell-specific markers, networks, metabolic pathways, and subpopulation enrichments were identified.
• A total of 298 common regulated genes associated with metabolic pathways were found across multiple cell types.
• Distinct adipocyte subpopulations were differentially involved in metabolic dysfunction.

Conclusions:

• vWAT exhibits significant cellular heterogeneity in its response to IH.
• Understanding these cell-specific responses provides crucial insights into OSA-related metabolic morbidity.
• These findings may lead to novel therapeutic strategies targeting vWAT in OSA.