Leptin Receptor Gene and Its Role in Obesity: A Comprehensive Narrative Review of Current Evidence
Keywords:
Leptin; Obesity; Gene; Receptor.Abstract
Background:
Obesity is a disorder of multiple factors and is influenced by the genetic, environmental, and behavioral
factors. The leptin receptor gene (LEPR) is the one that basically regulates the energy balance by being
the mediator of leptin signaling that is the controller of appetite and metabolism. The genetic variations
of LEPR are the major causes of resistance to leptin, which is the main mechanism that leads to obesity.
Objective:
This review exhaustively delves into the aspects of the LEPR gene such as its structure, function,
polymorphisms, and signaling pathways and also the role of the gene in the obesity pathogenesis,
accompanying metabolic disorders, and the prospects of therapy.
Methods:
The research findings from molecular, genetic, and clinical studies were discussed through a narrative
synthesis of evidence. The research mainly focused on the mechanistic aspects of the LEPR gene in
obesity, associations at population levels, and pharmacogenomic implications.
Results:
LEPR polymorphisms especially Q223R, K109R, and K656N alter the receptor affinity as well as the
subsequent JAK2–STAT3, MAPK, and PI3K signaling thus the susceptibility to obesity and the
metabolic effects. Epigenetic changes and chronic inflammation contribute to the aggravation of leptin
resistance. Besides, LEPR defect has also been proven to be the cause of type 2 diabetes, metabolic
syndrome, PCOS, and cardiovascular diseases. The newly proposed interventions comprise gene
therapy, correction through CRISPR, and RNA therapeutics aimed at leptin sensitization.
Conclusion:
The LEPR gene is one of the most important molecular factors that lead to obesity and disorders related
to it. The combination of genetic, epigenetic, and pharmacogenomic knowledge with personalized
obesity medicine has the power to bring about a complete change in the ways of prevention and treatment
through the restoration of leptin sensitivity and metabolic balance
