Emerging role of metabolic reprogramming in hyperoxia-associated neonatal diseases

Abstract

Oxygen therapy is common during the neonatal period to improve survival, but it can increase the risk of oxygen toxicity. Hyperoxia can damage multiple organs and systems in newborns, commonly causing lung conditions such as bronchopulmonary dysplasia and pulmonary hypertension, as well as damage to other organs, including the brain, gut, and eyes. These conditions are collectively referred to as newborn oxygen radical disease to indicate the multi-system damage caused by hyperoxia. Hyperoxia can also lead to changes in metabolic pathways and the production of abnormal metabolites through a process called metabolic reprogramming. Currently, some studies have analyzed the mechanism of metabolic reprogramming induced by hyperoxia. The focus has been on mitochondrial oxidative stress, mitochondrial dynamics, and multi-organ interactions, such as the lung-gut, lung-brain, and brain-gut axes. In this article, we provide an overview of the major metabolic pathway changes reported in hyperoxia-associated neonatal diseases and explore the potential mechanisms of metabolic reprogramming. Metabolic reprogramming induced by hyperoxia can cause multi-organ metabolic disorders in newborns, including abnormal glucose, lipid, and amino acid metabolism. Moreover, abnormal metabolites may predict the occurrence of disease, suggesting their potential as therapeutic targets. Although the mechanism of metabolic reprogramming caused by hyperoxia requires further elucidation, mitochondria and the gut-lung-brain axis may play a key role in metabolic reprogramming.

Keywords: Bronchopulmonary dysplasia; Hyperoxia; Metabolic reprogramming; Mitochondria; Neonate.