Leptin Resistance Signaling is a pathological state where the hypothalamus and other crucial target tissues exhibit a significantly diminished or entirely absent response to the potent appetite-suppressing and long-term energy-regulating effects of the hormone leptin. This fundamental resistance severely disrupts the homeostatic negative feedback loop designed to maintain energy balance, frequently resulting in persistent feelings of hunger, an increase in energy storage, and subsequent weight gain. It represents a core breakdown in the sophisticated communication system that governs metabolic stability.
Origin
The term integrates “leptin,” named from the Greek word leptos meaning “thin,” which refers to the satiety hormone secreted by fat cells, with “resistance,” denoting a lack of appropriate cellular response, and “signaling,” the process of biological communication. Its profound clinical relevance was fully recognized following the discovery of leptin and its central role in systemic energy homeostasis.
Mechanism
Leptin is released by adipocytes and acts primarily on receptors in the arcuate nucleus of the hypothalamus, where it activates the JAK-STAT signaling pathway to suppress the release of orexigenic neuropeptides. In Leptin Resistance Signaling, chronically high circulating leptin levels can lead to impaired transport across the blood-brain barrier or intracellular interference, such as the increased activity of SOCS3, which actively inhibits the JAK/STAT signaling cascade. This profound blockage prevents the brain from receiving the essential satiety signal, thereby perpetuating a state of chronic positive energy balance.
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