Integrating metabolomics into obesity care: towards biomarker- guided pharmacy practice

Abstract

Background: Obesity is a complex and prevalent global health issue strongly associated with chronic diseases. Early diagnosis and precise monitoring remain challenging due to the complex metabolic dysregulation underlying obesity. Metabolomics provides a powerful tool to investigate biochemical changes and discover novel diagnostic biomarkers. Objectives: This study used untargeted metabolomics of human plasma samples to identify distinct plasma metabolite profiles and altered metabolic pathways in overweight and obese individuals. The ultimate goal is to improve obesity management through early diagnosis and personalized treatments. Methods: A total of 74 Jordanian participants were recruited and categorized into normal-weight (n=29), overweight (n=17), and obese (n=28) groups based on BMI and metabolic parameters. Plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS). Data processing and statistical analysis were performed using MetaboScape and MetaboAnalyst 5.0. Group comparisons were evaluated using t-tests, ANOVA, and multivariate models, and pathway enrichment analysis was conducted to determine altered metabolic pathways. Results: A total of 82 metabolites were identified, with 26 showing significant differences between groups. In the overweight group, pantothenic acid and L-proline were elevated, while phenylacetaldehyde and glycerophosphocholine were decreased. The obese group exhibited increased levels of L-leucine, L-tryptophan, phenylalanine, and tyrosine, and reduced levels of 2,3-diaminopropionic acid and phenylacetaldehyde. Key altered pathways included pantothenate and CoA biosynthesis, beta-alanine metabolism, phenylalanine and tyrosine metabolism, and beta-oxidation of long-chain fatty acids. Conclusions: The study revealed significant novel metabolic disturbances associated with overweight and obesity, highlighting potential diagnostic biomarkers and perturbed metabolic pathways. These findings provide valuable insights into the molecular underpinnings of obesity, underscore the potential of metabolomics in advancing personalized approaches for managing obesity, and warrant further validation in larger, diverse populations to assess their diagnostic and clinical relevance.