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

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.

• Authors: Iris Lindberg, Lloyd D Fricker
• Journal: Endocrinology (Endocrinology) Vol. 162 Issue 12 (12 01 2021) ISSN: 1945-7170 [Electronic] United States
• PMID: 34333593 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Chemical References

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

Topics

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