Leptin Signaling and Genetic Polymorphisms in Metabolic Health
Summary
Leptin, an adipocyte-derived hormone, orchestrates energy balance by acting on the hypothalamus to suppress appetite and stimulate energy expenditure. Binding to its cognate receptor (LEPR) activates the JAK/STAT signalling cascade, with downstream effects on glucose homeostasis, lipid metabolism and inflammatory pathways. Genetic variations in the LEP and LEPR genes, notably single nucleotide polymorphisms (SNPs), modulate leptin production, receptor function and signal transduction efficiency. Such polymorphisms contribute to inter-individual differences in susceptibility to obesity, insulin resistance, type 2 diabetes and metabolic syndrome. Beyond energy regulation, leptin signalling influences cardiovascular risk factors and hepatic lipid handling, linking adiposity to systemic metabolic health. Recent advances have elucidated how common variants in LEPR (for example, rs1137101) alter receptor binding affinity and circulating leptin levels, while promoter-region SNPs in LEP (such as G2548A) affect gene transcription. These findings underscore the potential for genotype-guided interventions—ranging from metreleptin therapy to targeted lifestyle modifications—and highlight leptin signalling as a nexus for personalised strategies against metabolic disease.
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Leptin Signaling and Genetic Polymorphisms in Metabolic Health publication trend
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Technical terms
Leptin: Adipocyte-derived hormone that regulates appetite and energy expenditure.
Leptin receptor (LEPR): Cell-surface receptor that mediates leptin signalling via JAK/STAT pathways.
Single nucleotide polymorphism (SNP): A DNA sequence variation at a single nucleotide position among individuals.
Metabolic syndrome: A cluster of conditions—dyslipidaemia, hypertension, central obesity and hyperglycaemia—that increase cardiovascular and diabetes risk.
JAK/STAT pathway: Intracellular cascade triggered by receptor activation, leading to gene transcription changes in response to hormones and cytokines.
References
- Genetic predisposition of LEPR (rs1137101) gene polymorphism related to type 2 diabetes mellitus – a meta-analysis. Annals of Medicine (2023).
- LEP (G2548A-G19A) and ADIPOQ (T45G-G276T) gene polymorphisms are associated with markers for metabolic syndrome. Diabetology & Metabolic Syndrome (2023).
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