Metabolomics and Metabolic Diseases: Where Do We Stand?

Abstract

Metabolomics, or the comprehensive profiling of small molecule metabolites in cells, tissues, or whole organisms, has undergone a rapid technological evolution in the past two decades. These advances have led to application of metabolomics for defining predictive biomarkers for incident cardiometabolic diseases, and increasingly, as a blueprint for understanding their pathophysiologic mechanisms. Progress in this area and challenges for the future are reviewed here.

Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism

“…Alterations in amino acid pools in the setting of incomplete β-oxidation may be found related to anaplerosis, a compensatory process of amino acid mobilization and oxidation to replenish the TCA cycle and maintain oxidative metabolism. Amino acid anaplerosis is found in established obesity (40). Glutaminolytic amino acids are not only important in anaplerosis, but also in biosynthetic processes (as we found enriched in our global uMSC myocyte gene expression analysis).…”

Metabolomic Analysis in Heart Failure

“…12 The serum I t is thought that at least 6,500 low-molecular-weight metabolites exist in humans, and these metabolites have various important roles in biological systems in addition to proteins and genes. 1 Comprehensive assessment of endogenous metabolites is called metabolomics, and recent advances in this field have enabled us to understand the critical role of previously unknown metabolites or metabolic pathways in the maintenance of homeostasis under both physiological and stress conditions. Techniques of metabolomic analysis have been elegantly reported and reviewed elsewhere, 2-4 so the details will not be repeated here.…”

Precision medicine in diabetes: an opportunity for clinical translation

“…75,76 These findings are consistent with a model in which excess of BCAAs contributes to impaired efficiency of fatty acid oxidation, resulting in the accumulation of incompletely oxidized lipid species, perhaps of particular relevance in insulin resistance. 70 Whether these metabolite alterations are common to all patients with T2D or serve to identify specific subgroups requires further exploration.…”

“…68,69 During the last decade, metabolomics has emerged as an integrative tool for biological states through the global measurement of chemical endophenotypes that lie downstream of genomic, transcriptomic, and proteomic variability. 70 One key advantage of metabolomics is that the measured entity is closer to the organismal phenotype than genetic variation and integrates a number of biological processes; thus, the effect size on the trait of interest is typically larger. Disadvantages include the complex and incompletely characterized nature of the metabolome, the unknown nature of many measured metabolites, the diversity of technologies and data-analysis techniques used, and the correlational nature of most analyses where causal inference is challenging.…”