Candidate Obesity Biomarkers Identified Through Multi-Omics Analysis, Mendelian Randomization, and Mediation Analysis

Area of Science:

• Metabolomics
• Lipidomics
• Genetics
• Public Health

Background:

• Obesity is a global health crisis, driving metabolic disorders.
• Circulating biomarkers for obesity are known, but their causal links require clarification.
• Advanced metabolomic and lipidomic techniques offer new avenues for biomarker discovery.

Purpose of the Study:

• To identify and validate novel serum metabolites and lipids associated with obesity.
• To investigate the causal relevance of these biomarkers using Mendelian randomization (MR).
• To explore the potential mediation of immune cell traits and associations with cardiometabolic risk factors.

Main Methods:

• Untargeted UPLC-MS/MS metabolomics and LC-MS/MS lipidomics on serum samples from obese and non-obese individuals.
• Two-sample bidirectional Mendelian randomization (MR) and MR-based mediation analyses integrating GWAS data.
• Receiver operating characteristic (ROC) and regression analyses to assess biomarker performance and clinical associations.

Main Results:

• Hexanoylglycine and lysophosphatidylcholine (LPC (16:0)) were significantly altered in obese participants.
• MR analyses provided evidence for the potential causal relevance of these biomarkers to obesity.
• Both biomarkers correlated with obesity status, BMI, and blood pressure, with potential mediation by immune cell traits.

Conclusions:

• Hexanoylglycine and LPC (16:0) are promising candidate serum biomarkers for obesity.
• These biomarkers may play a role in obesity-related metabolic dysregulation and cardiometabolic risk.
• Further research can explore their utility in clinical settings for obesity management and risk assessment.