The metabolome profiling of obese and non-obese individuals: Metabolically healthy obese and unhealthy non-obese paradox

Document Type: Original Article


1 Department of Chemistry, Sharif University of Technology, Tehran, Iran

2 Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran

3 Chemical Injuries Research Center, Systems Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran


Objective(s): The molecular basis of “metabolically healthy obese” and “metabolically unhealthy non-obese” phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals.
Materials and Methods: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment analysis was performed to identify underlying pathways.
Results: Significantly higher levels of glutamine, asparagine, alanine, L-glutathione reduced, 2-aminobutyrate, taurine, betaine, and choline, and lower level of D-sphingosine were observed in MHO group compared with MUHO. In comparison of MHNO and MUHNO groups, significantly lower levels of alanine, glycine, glutamine, histidine, L-glutathione reduced, and betaine, and higher levels of isoleucine, L-proline, cholic acid, and carnitine appeared in MUHNO individuals. Moreover, significantly affected pathways included amino acid metabolism, urea cycle and ammonia recycling in MUHO subjects and glutathione metabolism, amino acid metabolism, and ammonia recycling in MUHNO members.
Conclusion: Literature review helped us to hint that altered levels of most metabolites might associate to insulin sensitivity and insulin resistance in MHO and MUHNO individuals, respectively. Besides, abnormal amino acid metabolism and ammonia recycling involved in unhealthy phenotypes (MUHO, MUHNO) might be associated with insulin resistance.


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