# A Preliminary Integrated Metabolomics Analysis Identifies Retrograde Endocannabinoid Signaling Shift in Severe OSA Patients

## TL;DR

This study finds that severe obstructive sleep apnea disrupts key metabolic pathways, including retrograde endocannabinoid signaling, which could explain its broader health effects.

## Contribution

The novel finding is the identification of retrograde endocannabinoid signaling pathway shifts in severe OSA patients through integrated metabolomics analysis.

## Key findings

- Severe OSA patients showed significant alterations in 59 GC–MS and 27 LC–MS metabolites.
- Retrograde endocannabinoid signaling was the only common pathway altered in both GC–MS and LC–MS data.
- Sleep fragmentation was linked to increased ROS production in severe OSA patients.

## Abstract

The systemic influence of obstructive sleep apnea(OSA), particularly in those with severe OSA (sOSA), has frequently been disregarded. An investigation was conducted to examine the variations of reactive oxygen species (ROS) and metabolomic drifts, as well as their interrelations, in adult OSA patients.

A total of 22 male patients were enrolled after undergoing polysomnography (PSG), and blood samples were obtained. Following the measurement of ROS levels in polymorphonuclear neutrophils (PMNs), plasma samples were combined and analyzed using both Gas Chromatography-Mass Spectrometry (GC–MS) and Liquid Chromatography-Mass Spectrometry (LC–MS).

Patients with sOSA had a higher body mass index (BMI) (p = 0.005) and more negative PSG measures compared to those with mild/moderate OSA (mOSA). Although there was no remarkable difference in neutrophil ROS between the mOSA and sOSA group, further analysis indicated sleep fragmentation was associated with ROS production(p = 0.043 for N3%, p < 0.01 for Arousal Index). Integrated metabolomics analysis revealed significant alterations in 59 metabolites from GC–MS and 27 metabolites from LC–MS in sOSA patients. These substantial changes perturbed various pathways, including the FoxO signaling pathway and its upstream PI3K-Akt signaling pathway, and so on. Notably, the retrograde endocannabinoid signaling pathway was the sole common pathway identified in both GC–MS and LC–MS data.

This study sheds light on the systemic impact of OSA, particularly in severe cases, by uncovering extensive disturbance of metabolic pathways. The identification of retrograde endocannabinoid signaling shifts in severe OSA adults highlights its potential impact in the sleep disorder and its broader repercussions in the body.