Leptin is an adipokine secreted proportional to fat mass. A patient with congenital leptin deficiency (Leptin gene mutation) has severe hyperphagia and obesity. The primary receptor through which leptin suppresses appetite is located in which hypothalamic nucleus, and on which type of neurons?

• A Lateral hypothalamus on MCH (melanin-concentrating hormone) orexigenic neurons
• B Arcuate nucleus on POMC/CART anorexigenic neurons (activated by leptin) and on NPY/AgRP orexigenic neurons (inhibited by leptin) ✓
• C Ventromedial hypothalamus on glucoreceptor neurons sensing blood glucose
• D Paraventricular nucleus on CRH neurons

Explanation

LepRb (long form of leptin receptor) is highly expressed in the arcuate nucleus. Leptin activates JAK2-STAT3 signalling in POMC/CART neurons, increasing alpha-MSH release, which acts on MC4R in the paraventricular nucleus to suppress appetite and increase energy expenditure. Simultaneously, leptin hyperpolarises and inhibits NPY/AgRP neurons in the same nucleus, reducing the orexigenic drive. Congenital leptin deficiency removes this brake on NPY/AgRP and removes POMC activation, causing voracious hyperphagia. The lateral hypothalamus MCH neurons and VMH glucoreceptors are not the primary arcuate leptin targets.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.