Leptin receptor (LEPR) (LEPR)

The Leptin receptor (LEPR) is a type I cytokine receptor that plays a pivotal role in the regulation of body weight and energy expenditure by mediating the effects of the hormone leptin (UniProt P48357). While its function in the hypothalamus is well-documented for controlling satiety, LEPR is also significantly expressed in oral sensory neurons, particularly within the taste receptor cells of the tongue (Shigemura et al., 2004, PubMed: 15513991). In these peripheral neurons, leptin functions as a specific modulator of taste, selectively suppressing the neural and behavioral responses to sweet stimuli without affecting other taste modalities (Kawai et al., 2000, PubMed: 11004354). This suppression is achieved through the activation of ATP-sensitive potassium (KATP) channels, which hyperpolarizes sweet-sensitive taste cells and decreases their excitability. Consequently, the leptin receptor in the oral cavity acts as a metabolic sensor that adjusts taste sensitivity based on the body's energy status, and its dysfunction is implicated in the development of obesity and altered eating behaviors (Niki et al., 2011, PubMed: 21673049). Therapeutic interventions targeting this receptor, such as metreleptin, are currently utilized for rare metabolic disorders, but the oral LEPR pathway remains a target of interest for broader applications in appetite control and obesity management.

Other names

OB-RCD295B219LEP-RLeptin receptor gene-related protein

Agonism of the leptin receptor (LEPR) activates the JAK2/STAT3 signaling pathway; specifically in oral sensory neurons, LEPR activation leads to the opening of ATP-sensitive potassium (KATP) channels, which hyperpolarizes sweet-responsive taste cells and reduces their sensitivity to sweet stimuli (Kawai et al., 2000; Shigemura et al., 2004).