Modulation of hepatic gene expression profiles by vitamin B₁, vitamin B₂, and niacin supplementation in mice exposed to acute hypoxia

Abstract

This study was aimed to observe the effects of vitamin B, vitamin B, and niacin supplementation on hepatic gene expression profiles in mice exposed to acute hypoxia. Thirty mice were randomly divided into normal, acute hypoxia, and acute hypoxia plus vitamin B, vitamin B, and niacin supplementation groups and fed corresponding diets for 2 weeks and then exposed to a simulated altitude of 6000 m for 8 h. Hepatic gene expression profiles were analyzed using a microarray technique. Several biochemical markers were also assayed. The results showed that a total of 2476 genes were expressed differentially after acute hypoxia exposure (1508 upregulated genes and 968 downregulated genes). Compared with the acute hypoxia group, there were 1382 genes differentially expressed (626 upregulated genes and 756 downregulated genes) in the acute hypoxia plus vitamin B, vitamin B, and niacin supplementation group. Pathway analysis indicated that carbohydrate, lipid, and amino acid metabolism, as well as electron transfer chain, were improved to some extent after vitamin B, vitamin B, and niacin supplementation. Supportive results were obtained from biochemical assays. Our findings suggest that the supplementation of vitamin B, vitamin B, and niacin is beneficial in improving nutritional metabolism partly via gene expression under acute hypoxia condition.

Preliminary screening of biomarkers in HAPE based on quasi-targeted metabolomics

“…Melatonin (MT) (Claustrat and Leston, 2015), which reduces the release of excitatory amino acids and which was significantly decreased in the body of the hypoxia group, further mediates the accumulation and neurotoxicity of excitatory amino acids and may even induce the occurrence of high-altitude cerebral edema (Ruan et al, 2000;Zhu and Xu, 2019). It is worth noting that a large number of B vitamins can reduce disorders of amino acid metabolism caused by hypoxia and that appropriate supplementation of vitamin B (VB) may play a certain role against hypoxic injury in the body (Liu et al, 2018). Our metabolome data results showed that VB2 in rat venous blood decreased significantly in HAPE, suggesting that VB2 levels may decrease exhaustively in a hypoxic environment.…”

“…It is worth noting that a large number of B vitamins can reduce disorders of amino acid metabolism caused by hypoxia and that appropriate supplementation of vitamin B (VB) may play a certain role against hypoxic injury in the body ( Liu et al, 2018 ). Our metabolome data results showed that VB2 in rat venous blood decreased significantly in HAPE, suggesting that VB2 levels may decrease exhaustively in a hypoxic environment.…”

Breath of Fresh Air: Toward Unraveling the Molecular Underpinnings of Sleep Apnea

“…Using CRISPR–Cas9 gene editing, a point mutation knock-in mouse (Slc52a3P258L) was generated that showed higher riboflavin concentrations and downregulation of a number of lipid-associated metabolites in brain tissue, consistent with hyperlipidemia in the livers of Slc52a3 knockout mice ( 11 ). Of note, however, under exposure to chronic intermittent hypoxia, no metabolic changes were seen between wild-type and Slc52a3P258L mice, despite prior gene changes observed under acute hypoxia that were partially rescued with supplements including riboflavin ( 9 ).…”

“…There are multiple potential mechanisms in which riboflavin deficiency could impact OSA. Additional riboflavin appears to be required under acute hypoxic conditions ( 9 ). Riboflavin is the precursor of flavin adenine dinucleotide, a coenzyme that affects HIF1A stability ( 10 ).…”