Plasma metabolites may inhibit childhood obesity by regulating ferroptosis through SMPD1 and SIRT3
Authors' conclusion
This study is the first to reveal, through Mendelian randomization analysis, the potential mediating role of ferroptosis-related genes in the association between plasma metabolites and childhood obesity. It suggests that the ferroptosis mechanism may influence childhood obesity risk by regulating specific metabolites. These findings contribute to understanding the role of ferroptosis in the pathological mechanisms of childhood obesity and provide novel molecular targets and intervention strategies for obesity prevention and treatment in children.
Study context
- Population
- Publicly available genome-wide association study (GWAS) datasets: 1400 plasma metabolites, 159 ferroptosis-related genes and childhood obesity
- Outcome
- Childhood obesity
Methodological detailsbidirectional two-step Mendelian randomization, GWAS datasets, inverse-variance weighted method, MR-PRESSO
- Bidirectional two-step Mendelian randomization
- GWAS datasets
- Inverse-variance weighted method
- MR-PRESSO
Main finding
As reported in the abstract
Ferroptosis-related genes significantly associated with childhood obesity (SMPD1 and SIRT3 suppressing, GSTZ1 and ADAMTS13 promoting obesity)
4
Plasma metabolites significantly associated with childhood obesity (6 negatively, 3 positively correlated)
9
Highest mediation proportion of metabolite–childhood obesity association by SMPD1- and SIRT3-regulated ferroptosis (partial mediation)
9.62%
Further findings
Sensitivity analysis and reverse Mendelian randomization (MR)
- Results robust (no heterogeneity or horizontal pleiotropy); reverse Mendelian randomization ruled out causal interference
Original publication
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