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Published on: May 6, 2022
Integrative multi-omics analysis reveals molecular signatures of central obesity in children
Chengzhi Zhao1,2, Xizhou An1, Leyuan Xiao1
1Department of Epidemiology and Biostatistics, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, China.
Insights
This study identified key lipids and proteins, including PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB, as potential biomarkers for childhood central obesity. These findings may help develop new interventions to prevent childhood obesity and its associated health risks.
Area of Science:
- Metabolomics and Proteomics
- Pediatric Endocrinology
- Cardiovascular Disease Risk Factors
Background:
- Central obesity in children is linked to hypertension and coronary heart disease.
- The underlying molecular mechanisms of childhood central obesity require further investigation.
- Understanding these mechanisms is crucial for early intervention and prevention strategies.
Purpose of the Study:
- To investigate specific lipids and proteins associated with childhood central obesity.
- To explore the molecular pathways contributing to the development of central obesity in children.
- To identify potential biomarkers for early detection and therapeutic targets.
Main Methods:
- A case-control study involving 169 children (aged 7-16 years) with and without central obesity.
- Plasma lipidomics and proteomics analyses were performed on human samples.
- Comparative lipidomics and transcriptomics analyses were conducted on mouse liver samples under different feeding conditions.
Main Results:
- Forty-six key lipids, primarily triglycerides (TAG) and diacylglycerols (DAG), were significantly associated with central obesity.
- Six proteins (PLIN1, PLAT, ADH1A, ADH4, LEP, INHB) showed increased plasma expression in children with central obesity.
- Mouse liver studies revealed some overlapping differential lipids but minimal overlap in differential genes compared to human data, highlighting species and methodological differences.
Conclusions:
- PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB are identified as potential significant biomarkers for childhood central obesity.
- These biomarkers may influence the central obesity phenotype by modulating lipid levels (TAG, DAG, LDL-C, HDL-C).
- The study provides novel insights into the molecular mechanisms of childhood central obesity, offering potential targets for intervention.
Background:
Central obesity is associated with an increased risk of hypertension and coronary heart disease. However, its molecular mechanisms have not yet been fully understood. This study aims to investigate lipids and proteins related to childhood central obesity, exploring the molecular mechanisms underlying this condition.
Methods:
A case-control study was conducted, including a total of 169 children (aged 7-16 years, 53.25% male, and 74 children in the central obesity group). Plasma lipidomics were measured in all 169 children, and plasma proteomics was measured in 112 of these children. The transcriptomics and lipidomics of the mice's liver were measured for normal feed and high-fat feed mice.
Results:
Forty-six key lipids significantly associated with central obesity were identified, predominantly triglycerides (TAG), with a minority being diacylglycerols (DAG). Additionally, six key proteins, namely PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB, were discovered, which may positively influence the central obesity phenotype by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C. These proteins exhibited increased expression in the plasma of children with central obesity. Validation using mouse liver samples showed some overlapping differential lipids between mice and children, albeit minimal overlap in differential genes. This discrepancy may stem from inherent differences between transcriptomics and proteomics, species variations, and differing sampling sites.
Conclusions:
PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB are potential significant biomarkers for childhood central obesity and may influence the phenotype of childhood central obesity by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C.
Impact:
PLIN1, PLAT, ADH1A, ADH4, LEP, and INHB are potentially significant biomarkers for childhood central obesity and may influence the phenotype of childhood central obesity by modulating levels of lipids such as TAG, DAG, LDL-C, and HDL-C. Research on integrating lipidomics and proteomics to elucidate the mechanisms of obesity, especially childhood central obesity, remains extremely limited. Our study filled this gap. Our findings highlight potential biomarkers and therapeutic targets that could pave the way for new interventions and treatments to prevent central obesity in children and its harm.
