Leptin and adiponectin receptor signaling

Leptin and adiponectin receptor signaling represents the integrated endocrine axis through which adipose tissue communicates with the central nervous system and peripheral tissues to regulate energy homeostasis and insulin sensitivity. Leptin, acting through the leptin receptor (LEPR), primarily modulates the JAK2/STAT3 pathway in the hypothalamus to suppress appetite and increase metabolic rate (UniProt P48357). Adiponectin signals through ADIPOR1 and ADIPOR2 to activate AMPK and PPAR-alpha, promoting fatty acid oxidation and glucose uptake while exerting potent anti-inflammatory effects (UniProt Q96A54). Dysregulation of this axis, typically manifesting as leptin resistance and hypoadiponectinemia, is a central driver of obesity-related pathologies, including type 2 diabetes and nonalcoholic fatty liver disease (PubMed: 28214560). While metreleptin is an FDA-approved therapy for lipodystrophy, the broader therapeutic potential of this axis is being explored through adiponectin mimetics and leptin sensitizers (Nature: 10.1038/nature12744). The leptin-to-adiponectin ratio is increasingly utilized as a clinical biomarker for metabolic syndrome and cardiovascular risk assessment (PubMed: 30103444). Therapeutic challenges include the high prevalence of leptin resistance in common obesity and the risk of developing neutralizing antibodies during treatment with recombinant analogs (FDA: Myalept Label).

Other names

Adipokine signaling pathwayLeptin-Adiponectin axisAdipose-derived hormone signaling

Activation of the JAK2/STAT3 pathway via the leptin receptor to regulate satiety and energy expenditure, and activation of AMPK and PPAR-alpha pathways via adiponectin receptors to enhance insulin sensitivity and lipid metabolism.