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

Iris Lindberg, Lloyd D. Fricker

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numberbqab155
JournalEndocrinology
Volume162
Issue number12
DOIs
StatePublished - Dec 1 2021

Keywords

  • PC1/3
  • PC2
  • POMC
  • carboxypeptidase E
  • obesity
  • proprotein convertase

ASJC Scopus subject areas

  • Endocrinology

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