Leptin released from adipocytes reaches the hypothalamus during periods of energy abundance. The signal transduction pathway by which leptin suppresses appetite is best described as:
- A Nuclear receptor binding a hormone response element in promoter DNA
- B Gs-coupled receptor increasing intracellular cAMP
- C JAK2-STAT3 pathway acting through a cytokine-family receptor ✓
- D Receptor serine-threonine kinase activating SMAD transcription factors
Correct answer: C. JAK2-STAT3 pathway acting through a cytokine-family receptor
Explanation
Leptin acts on long-form leptin receptors in arcuate nucleus neurons. This receptor is a class I cytokine receptor structurally related to the GH receptor: it has no intrinsic kinase but constitutively associates with JAK2, which autophosphorylates on ligand binding and activates STAT3. Phosphorylated STAT3 enters the nucleus and drives anorexigenic neuropeptides such as POMC while suppressing NPY and AgRP. Nuclear receptors and SMAD pathways belong to steroids and TGF-beta respectively, not leptin.
Reference: Harper's Illustrated Biochemistry, 31st ed.
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