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Exploring LEPR-Linked Metabolic Diversity through Gut Microbiome-Metabolome Network Analysis in Non-Obese Adults
Kyeong-Seog Kim1,2,3, Joo-Youn Cho1,2,4, Ye Chan Park5,6
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Biomolecules & Therapeutics
|February 27, 2026
Summary
Genetic variations in the leptin receptor (LEPR) gene influence metabolic health by altering gut microbiome and serum metabolite profiles in healthy adults. These interactions highlight indirect genetic effects on metabolism.
Area of Science:
- Metabolomics
- Genetics
- Microbiome Research
Background:
- Leptin receptor (LEPR) gene variations impact metabolic regulation.
- Gut microbiome and serum metabolites are key mediators of host metabolic phenotype.
- Systems-level interactions between LEPR genotypes, gut microbes, and metabolomic profiles are not well understood.
Purpose of the Study:
- To investigate the associations between LEPR genotypes, gut microbial composition, and serum metabolomic profiles in healthy Korean adults.
- To explore the network-level interactions among these components and their influence on metabolic phenotypes.
Main Methods:
- Cross-sectional study of 37 healthy Korean adults.
- Genotyping of three LEPR single nucleotide polymorphisms (SNPs).
- Untargeted serum metabolomics via GC-TOF-MS and gut microbiome profiling via 16S rRNA sequencing.
- Statistical and network analyses using Cytoscape.
Main Results:
- LEPR genotypes (rs1137101, rs1173100) correlated with specific serum metabolites like pimelic acid and malonic acid.
- Gut microbial phyla showed differential correlations with metabolites (e.g., Firmicutes with fatty acids, Actinobacteria with cholesterol).
- Network analysis identified indole-3-acetate and cholesterol as central nodes, linking microbes to host factors like BMI and leptin levels.
Conclusions:
- LEPR genetic variation is linked to distinct serum metabolomic patterns and microbiome-host networks in healthy individuals.
- No direct molecular pathways involving leptin signaling were identified.
- Network associations suggest indirect genetic influences on metabolic states via microbiome-metabolome interactions, advancing personalized metabolic regulation insights.
