Comprehensive Analysis of Serum Metabolites and Whole Blood Cell Transcriptome reveals the Dysregulated Metabolic Pathways in Metabolically Healthy Obesity.

Background Obesity stands as a formidable public health challenge, contributing to a spectrum of diseases, including cardiovascular disorders, and type 2 diabetes mellitus. Individuals with obesity classified as “metabolically healthy” have susceptibility to various diseases later in life. These diseases often linked to dysregulated metabolic pathways. Our objective was to explore potential associations between serum metabolites and features of metabolic diseases in metabolically healthy subjects with obesity. Methods We analyzed a dataset of 40 subjects with obesity only (OBO, n = 20) versus age-matched lean healthy controls (LHC, n = 20). We measured 711 serum metabolites and whole blood transcriptomes. Pathway enrichment analysis was employed to uncover meaningful insights into the association between metabolite concentrations and the observed phenotypic changes. Finally, Transcriptome profiling and subsequent gene set enrichment was done to identify the differentially enriched pathways between the LHC to OBO subjects. Results A total of 116 metabolites, mostly lipids, were significantly different (p < 0.05) between the 2 groups. Notably the metabolites demonstrated a distinct metabolic signature differentiating OBO from LHC group. The differentially expressed metabolites include lipids, amino acids, nucleotides, peptides, partially characterized molecules, cofactors/vitamins, carbohydrates, xenobiotics, and energy-related metabolites. Pathway enrichment scores indicated that out of 26 metabolic pathways,14 pathways were differentially activated between the 2 groups. Among these, 5 major metabolic pathways significantly enriched and had maximum difference in mean activity between the two groups were aminoacyl-tRNA biosynthesis, phosphonate and phosphinate metabolism, pyrimidine metabolism, glutathione metabolism and lysine degradation. Conclusions Our results indicate that obesity is characterized by a distinctive metabolomic signature emphasizing the perturbed pathways involving amino acids and lipid metabolism.