Leptin Receptor Sensitivity is the measure of how effectively target cells, primarily in the hypothalamus, respond to the circulating levels of the adipokine leptin. Leptin is a key chronic energy signal, and optimal sensitivity is critical for the appropriate central interpretation of long-term energy sufficiency, leading to appetite suppression and maintenance of metabolic rate. Diminished sensitivity, often termed leptin resistance, is a significant feature of metabolic dysfunction and obesity, as the brain fails to register high energy stores, leading to unmitigated hunger and reduced energy expenditure.
Origin
This term is a clinical and molecular concept that emerged following the discovery of the hormone leptin and its receptor (Ob-R) in the mid-1990s. Sensitivity is a core pharmacological concept describing the degree of cellular response to a signaling molecule.
Mechanism
Leptin binds to its receptor, Ob-Rb, on Pro-opiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus, initiating an intracellular signaling cascade, primarily via the JAK-STAT pathway. Effective signaling leads to the transcription of anorexigenic neuropeptides, promoting satiety. Reduced sensitivity occurs when chronic, high levels of leptin lead to a blunting of this intracellular signaling cascade, a process often associated with endoplasmic reticulum stress and inflammation. Consequently, despite abundant energy stores, the brain interprets the signal as a state of starvation, resulting in persistent orexigenic drive.
We use cookies to personalize content and marketing, and to analyze our traffic. This helps us maintain the quality of our free resources. manage your preferences below.
Detailed Cookie Preferences
This helps support our free resources through personalized marketing efforts and promotions.
Analytics cookies help us understand how visitors interact with our website, improving user experience and website performance.
Personalization cookies enable us to customize the content and features of our site based on your interactions, offering a more tailored experience.