Targeted Metabolic Profiling of Plasma in Lean and Obese Individuals during Oral Glucose Ingestion

Abstract

Obesity has long been associated with metabolic inflexibility and insulin resistance. The purpose of this study was to determine 1) if the plasma metabolite/lipid profile was altered during an oral glucose tolerance test (OGTT) with obesity and 2) whether changes in plasma metabolites/lipids were related to insulin sensitivity or metabolic flexibility. Fourteen (7M/7F), young, lean (BMI: 21.9 ± 1.8 kg/m2) and fourteen (7M/7F) young, obese (BMI: 40.6 ± 5.4 kg/m2) individuals underwent a 2-hour OGTT with plasma samples obtained at baseline, 45 min and 120 min. Plasma was immediately stored at -80°C for subsequent targeted metabolomics (Biocrates MxP® Quant 500, Biocrates Life Sciences AG, Innsbruck, Austria). A 2 (body composition group) x 3 (time point) ANOVA was performed for each sex, with the false discovery rate (FDR q-value <0.10) used to account for multiple testing. Of the 73 small molecule metabolites tested, 2 (Glucose and Glutamate) differed between lean and obese females, and 34 metabolites (including 10 amino acids, 9 amino acid related, 5 bile acids, 2 biogenic amines and 2 carboxylic acids) changed with time in females. Of the 427 plasma lipid species tested, 79 (primarily triglycerides, TG) differed between lean and obese females, and 134 (primarily fatty acids and TG) changed with time. In males, 45 metabolites (similar to females) and 5 lipid species (Fatty acids only) changed with time. When examining the change in all plasma metabolites/lipid species from baseline to 120 min, the change in 9 TGs, 1 dihexosylceramide, as well as glycolithocholic acid sulfate (bile acid) were related to insulin sensitivity (Matsuda Index). Metabolic flexibility (change in respiratory exchange ratio from baseline to 120 min) was related to the change in 4 lysophosphatidylcholines, 3 TG, 2 acylcarnitines, 2 diglycerides, 3-Indoleacetic acid and glutamate. American Heart Association Grant: 18AIREA33960404. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.