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. 2022 Apr 29;13:832911. doi: 10.3389/fendo.2022.832911

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Copyright © 2022 Šket, Kotnik, Bizjan, Kocen, Mlinarič, Tesovnik, Debeljak, Battelino and Kovač

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Hypothalamic leptin-melanocortin system. The first in the cascade is the anorexigenic hormone leptin, whose blood level corresponds to the mass of white adipose tissue and which acts as a leptin receptor (LEPR) agonist. LEPR is further linked to differential neuronal involvement of neuropeptide Y (NPY)/agouti-related neuropeptide (AgRP) and proopiomelanocortin (POMC), with no inhibition by NPY/AgRP, POMC, on the other hand, [via its proprotein convertase subtilisin/kexin type 1/2 (PCSK1/2) cleavage activity] stimulates the melanocortin-4 receptor (MC4R) and the melanocortin-3 receptor (MC3R), ultimately leading to increased energy expenditure and decreased satiety.