Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models

Endocrinology. 2021 Dec 1;162(12):bqab155. doi: 10.1210/endocr/bqab155.


Peptides derived from proopiomelanocortin (POMC) are well-established neuropeptides and peptide hormones that perform multiple functions, including regulation of body weight. In humans and some animals, these peptides include α- and β-melanocyte-stimulating hormone (MSH). In certain rodent species, no β-MSH is produced from POMC because of a change in the cleavage site. Enzymes that convert POMC into MSH include prohormone convertases (PCs), carboxypeptidases (CPs), and peptidyl-α-amidating monooxygenase (PAM). Humans and mice with inactivating mutations in either PC1/3 or carboxypeptidase E (CPE) are obese, which was assumed to result from defective processing of POMC into MSH. However, recent studies have shown that selective loss of either PC1/3 or CPE in POMC-expressing cells does not cause obesity. These findings suggest that defects in POMC processing cannot alone account for the obesity observed in global PC1/3 or CPE mutants. We propose that obesity in animals lacking PC1/3 or CPE activity depends, at least in part, on deficient processing of peptides in non-POMC-expressing cells either in the brain and/or the periphery. Genetic background may also contribute to the manifestation of obesity.

Keywords: PC1/3; PC2; POMC; carboxypeptidase E; obesity; proprotein convertase.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Carboxypeptidases / physiology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Obese
  • Mixed Function Oxygenases / physiology*
  • Multienzyme Complexes / physiology*
  • Obesity / etiology*
  • Obesity / metabolism
  • Obesity / pathology
  • Pro-Opiomelanocortin / physiology*
  • Proprotein Convertase 2 / physiology
  • Proprotein Convertases / physiology*


  • Multienzyme Complexes
  • Pro-Opiomelanocortin
  • Mixed Function Oxygenases
  • peptidylglycine monooxygenase
  • Carboxypeptidases
  • Proprotein Convertases
  • PCSK2 protein, human
  • Proprotein Convertase 2