Beyond being an energy storage depot, white adipose tissue is now appreciated as a metabolically active, complex organ, with crucial roles in maintaining metabolic homeostasis. Untargeted metabolomic evaluation of white adipose tissue was undertaken to understand its metabolomic profile in individuals with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM).
Adult NGT (22 males, 26 females) and T2DM (19 males, 23 females) subjects undergoing laparoscopic surgeries (for gall stone, hernia, appendicitis, pancreatitis, splenic cyst or Achalasia cardia) were recruited with written, informed consent. Omental adipose tissue was snap-frozen and stored (-80°C). Untargeted metabolomic analysis was done using the Vanquish Ultra High Pressure Liquid Chromatography system and detection in positive and negative mode with the Orbitrap Eclipse Fusion Tribrid Mass spectrometer (Thermo Scientific Inc.). Downstream processing of the ions and identification of the lipids/small molecules was done using the Compound Discoverer software. After removal of duplicates/multiple entries, 3060 lipids/metabolites were annotated. Chemometric and univariate analysis was done with MetaboAnalyst 6.0. NGT and T2DM subjects were similar in age (48.7±6.5 and 49.4±7.0 respectively, P=0.630) and BMI (26.3±4.5 and 28.2±5.9 kg/m2 respectively, P=0.109). Supervised multivariate approach (Partial Least Square-Discriminant Analysis) could separate the NGT and T2DM groups based on these metabolites better than the unsupervised multivariate approach (Principal Component Analysis). Relative abundances of 365 lipids/small molecules were different between NGT and T2DM groups (P<0.05, t-test). These included amino acids, dipeptides, vitamins and their metabolites, citric acid cycle metabolites, carnitines, lysophosphocholines, lysophosphoethanolamines, N-acyl-amides and many medications/drugs.
This is the first untargeted metabolomic study of human adipose tissue from South Asian Indian diabetic subjects. Future studies that identify overlap between the diabetic adipose and plasma metabolome, and integrate genomic, epigenomic and exposome regulators of these profiles will help in unbiased understanding of novel, druggable adipose-specific molecular pathways in T2DM in South Asian Indians.