Metabonomic profiling of chronic intermittent hypoxia in a mouse model

Respir Physiol Neurobiol. 2018 Oct:256:157-173. doi: 10.1016/j.resp.2018.02.015. Epub 2018 Mar 6.

Abstract

Chronic intermittent hypoxia (ChIH) is a dominant feature of obstructive sleep apnoea (OSA) and is associated to metabolic alterations and oxidative stress (OS). Although management of OSA is well established, the research of new biomarkers that are independent of confounding factors remains necessary to improve the early detection of comorbidity and therapeutic follow-up. In this study, the urinary metabonomic profile associated to intermittent hypoxia was evaluated in a mouse model. When exposed to intermittent hypoxia, animals showed a significant alteration in energy metabolism towards anaerobic pathways and signs of OS imbalance. A compensatory response was observed over time. Our data also indicates an excess production of vitamin B3, liver function modulations and a stimulation of creatine synthesis which could be used to evaluate the ChIH repercussions. As well, TMAO and allantoin could constitute interesting biomarker candidates, respectively in the context of cardiovascular risk and OS associated to OSA.

Keywords: Intermittent hypoxia; Metabonomic; Obstructive sleep apnoea; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Creatine / metabolism
  • Disease Models, Animal
  • Glucose Tolerance Test
  • Guanidinoacetate N-Methyltransferase / metabolism
  • Hypoxia / urine*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Magnetic Resonance Spectroscopy / methods
  • Metabolomics / methods*
  • Mice
  • Oxidative Stress / physiology*
  • Time Factors
  • Tritium / metabolism

Substances

  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tritium
  • Guanidinoacetate N-Methyltransferase
  • Creatine