Characterizing substrate utilization during the fasted state using plasma high-resolution metabolomics

Area of Science:

• Metabolomics
• Human Physiology
• Nutritional Science

Background:

• High-resolution metabolomics offers a global view of metabolites and pathways in physiological processes.
• Substrate utilization during fasting is a key metabolic state, clinically assessed by respiratory exchange ratio (RER).

Purpose of the Study:

• To utilize metabolomics to identify metabolic pathways and plasma metabolites associated with substrate utilization in healthy, fasted adults.
• To explore the relationship between RER and the fasting plasma metabolome.

Main Methods:

• A cross-sectional study involving 33 healthy adults after an overnight fast.
• Indirect calorimetry was used to measure resting respiratory exchange ratio (RER).
• Untargeted metabolomics on plasma samples using dual-column liquid chromatography and ultra-high-resolution mass spectrometry.

Main Results:

• Respiratory exchange ratio (RER) was significantly associated with 1389 metabolites within 13 metabolic pathways (P < 0.05).
• Key pathways identified include fatty acid activation, C21-steroid hormone biosynthesis, butyrate metabolism, carnitine shuttle, glucogenic amino acids, methionine and cysteine metabolism, galactose, and pyrimidine metabolism.
• These findings highlight the involvement of lipid, amino acid, and carbohydrate metabolism in substrate utilization.

Conclusions:

• The fasting plasma metabolome reflects diverse macronutrient pathways in healthy adults.
• Metabolomics can provide insights into individual nutrient requirements.
• Further research should compare these findings in clinical populations.