Background Obesity, widely recognized as a serious health concern, is characterized by profoundly altered metabolism. However, the intermediate metabolites involved in this change remain largely unknown. Objective: We conducted targeted metabolomics profiling to identify moieties associated with adult obesity. Methods In this case-control study of Iranian adults, 200 obese patients were compared with 100 controls based on 104 metabolites profiled by a targeted metabolomic approach using liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS). The analysis comprised acylcarnitines, diacyl-phosphatidylcholines (PCaa), acyl-alkyl-phosphatidylcholines (PCae), sphingomyelins (SM), lyso-phospholipids (LPC) and amino acids. We performed multivariable linear regression to identify metabolites associated with obesity, adjusting for age, sex, total energy intake, total physical activity, smoking, and alcohol consumption. The Bonferroni correction was used to adjust for multiple testing. Results A pattern of 19 metabolites was significantly associated with obesity. Branched chain amino acids, alanine, glutamic acid, proline, tyrosine LPCa C16:1, PCaa C32:1, PCaa C32:2 and PCaa C38:3 were positively, while serine, asparagine, LPCa C18:1, LPCa C18:2, LPCe C18:0, PCae C34:3, PCae C38:4 and PCae C40:6 were negatively associated with obesity (all p < 0.00048). Conclusions A metabolomic profile containing 9 amino acids and 10 polar lipids may serve as a potential biomarker of adult obesity. Further studies are warranted to replicate these findings as well as investigate potential changes in this profile after weight reduction.

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A particular subgroup of obese adults, considered as metabolically healthy obese (MHO), has a reduced risk of metabolic complications. However, the molecular basis contributing to this healthy phenotype remains unclear. The objective of this work was to identify obesity-related metabolite patterns differed between MHO and metabolically unhealthy obese (MUHO) groups and examine whether these patterns are associated with the development of cardiometabolic disorders in a sample of Iranian adult population aged 18-50 years. Valid metabolites were defined as metabolites that passed the quality control analysis of the study. In this case-control study, 104 valid metabolites of 107 MHO and 100 MUHO patients were separately compared to those of 78 normal-weight metabolically healthy (NWMH) adults. Multivariable linear regression was used to investigate all potential relations in the study. A targeted metabolomic approach using liquid chromatography coupled to triple quadrupole mass spectrometry was employed to profile plasma metabolites. The study revealed that, after Bonferroni correction, branched-chain amino-acids, tyrosine, glutamic acid, diacyl-phosphatidylcholines C32:1 and C38:3 were directly and acyl-carnitine C18:2, acyl-lysophosphatidylcholines C18:1 and C18:2, and alkyl-lysophosphatidylcholines C18.0 were inversely associated with MHO phenotype. The same patterns were observed in MUHO patients except for the acyl-carnitine and lysophosphatidylcholine profiles where acyl-carnitine C3:0 and acyl-lysophosphatidylcholine C16:1 were higher and acyl-lysophosphatidylcholines C18:1, C18:2 were lower in this phenotype. Furthermore, proline, and diacyl-phosphatidylcholines C32:2 and C34:2 were directly and serine, asparagines, and acyl-alkyl-phosphatidylcholine C34:3 were negatively linked to MUHO group. Factors composed of amino acids were directly and those containing lysophosphatidylcholines were inversely related to cardiometabolic biomarkers in both phenotypes. Interestingly, the diacyl-phosphatidylcholines-containing factor was directly associated with cardiometabolic disorders in the MUHO group. A particular pattern of amino acids and choline-containing phospholipids may aid in the identification of metabolic health among obese patients.