Hypoxia Tissue Metabolomics
| Metabolite | log₂FC | p-value | −log₁₀(p) | Direction |
|---|
Background
Oxygen is the substrate for over 400 known biochemical reactions, surpassing even ATP and NADH. Notably, the leading causes of death in developed nations are due to impaired oxygenation – heart disease, stroke, and respiratory disease. One goal of the Jain Lab is to understand which metabolic processes fail as a function of oxygen tension and which pathways are successfully rewired to cope with variations in oxygen levels. To this end, in the present study, we sought to understand both acute and chronic variation in the metabolome as a result of modulating oxygen tension.
Experimental Design
The goal of this global metabolomic and complex lipid profiling study was to investigate the metabolic changes associated with impact of oxygen tension. Metabolon performed global metabolic profiling on brain, liver, heart, lung, muscle, plasma, and epididymal white adipose tissue (eWAT) samples from mice exposed to different conditions with varying oxygen tensions, durations and pharmacological treatment. Samples were collected from animals exposed to varying percentages of environmental oxygen, over a period between 3 hours and 3 weeks. Some animals were also administered FG-4592 (100 mg/kg, twice over 24h), a drug which acts as a HIF prolyl-hydroxylase inhibitor and thereby increases endogenous production of erythropoietin and stimulates the production of hemoglobin and red blood cells. Samples from each group were loaded in an equivalent manner, by mass, across the global metabolomic (HD4) profiling platform. The resulting data from the HD4 platform were median-scaled and minimum imputed prior to statistical analysis. Metabolite names that start with “X-“ are unknown compounds.
Data Analysis
Time Courses
Displays the abundance of a metabolite of interest by oxygen tension, timepoint, and tissue, scaled to the median.
Inputs
- Metabolite of interest – Select the metabolite you wish to analyze
- Reference group – Select the condition you wish to set as the reference
- Scale – Linear or Log2
Volcano Plot
For a given tissue, oxygen tension, and time point, plots all metabolites by fold change and p-value. This allows the user to identify the metabolites with the greatest statistically-significant changes in abundance.
Inputs
- Label metabolites – Metabolites entered here will be labeled and colored orange on the plot
- Tissue
- Condition A
- Condition B
- -Log10(P) Cutoff – Colors metabolites above this cutoff and includes them in the table below
- |Log2FC| Cutoff – Colors metabolites outside of this cutoff and includes them in the table below
Heat Map
For a particular metabolite, displays change in abundance compared to the reference condition (fold change) by oxygen tension, timepoint, and tissue. Hides color for conditions that are not statistically significant.
Input
- Metabolite
- Reference Condition
- P-Value Cutoff