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

Kaitlin R Taibl; Moriah P Bellissimo; Matthew Ryan Smith; Ken H Liu; ViLinh T Tran; Dean P Jones; Thomas R Ziegler; Jessica A Alvarez

doi:10.1016/j.nut.2023.112160

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

Nutrition. 2023 Dec:116:112160. doi: 10.1016/j.nut.2023.112160. Epub 2023 Jul 13.

Authors

Kaitlin R Taibl¹, Moriah P Bellissimo², Matthew Ryan Smith³, Ken H Liu³, ViLinh T Tran³, Dean P Jones³, Thomas R Ziegler⁴, Jessica A Alvarez⁵

Affiliations

¹ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States.
² Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States.
³ Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States.
⁴ Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, Georgia, United States.
⁵ Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, Georgia, United States. Electronic address: jessica.alvarez@emory.edu.

PMID: 37566924
PMCID: PMC10787037 (available on 2024-12-01)
DOI: 10.1016/j.nut.2023.112160

Abstract

Objectives: High-resolution metabolomics enables global assessment of metabolites and molecular pathways underlying physiologic processes, including substrate utilization during the fasted state. The clinical index for substrate utilization, respiratory exchange ratio (RER), is measured via indirect calorimetry. The aim of this pilot study was to use metabolomics to identify metabolic pathways and plasma metabolites associated with substrate utilization in healthy, fasted adults.

Methods: This cross-sectional study included 33 adults (mean age 27.7 ± 4.9 y, mean body mass index 24.8 ± 4 kg/m²). Participants underwent indirect calorimetry to determine resting RER after an overnight fast. Untargeted metabolomics was performed on fasted plasma samples using dual-column liquid chromatography and ultra-high-resolution mass spectrometry. Linear regression and pathway enrichment analyses identified pathways and metabolites associated with substrate utilization measured with indirect calorimetry.

Results: RER was significantly associated with 1389 metabolites enriched within 13 metabolic pathways (P < 0.05). Lipid-related findings included general pathways, such as fatty acid activation, and specific pathways, such as C21-steroid hormone biosynthesis and metabolism, butyrate metabolism, and carnitine shuttle. Amino acid pathways included those central to metabolism, such as glucogenic amino acids, and pathways needed to maintain reduction-oxidation reactions, such as methionine and cysteine metabolism. Galactose and pyrimidine metabolism were also associated with RER (all P < 0.05).

Conclusions: The fasting plasma metabolome reflects the diverse macronutrient pathways involved in carbohydrate, amino acid, and lipid metabolism during the fasted state in healthy adults. Future studies should consider the utility of metabolomics to profile individual nutrient requirements and compare findings reported here to clinical populations.

Keywords: Energy; Indirect calorimetry; Metabolism; Metabolomics; Nutrition; Substrate utilization.

MeSH terms

Adult
Amino Acids* / metabolism
Cross-Sectional Studies
Humans
Metabolome
Metabolomics* / methods
Pilot Projects
Young Adult

Substances

Amino Acids

Abstract

MeSH terms

Substances

Grants and funding