Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.
Iris LindbergLloyd D FrickerPublished in: Endocrinology (2022)
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.
Keyphrases
- high fat diet induced
- weight loss
- metabolic syndrome
- insulin resistance
- type diabetes
- weight gain
- body weight
- induced apoptosis
- adipose tissue
- bariatric surgery
- cell cycle arrest
- skeletal muscle
- gene expression
- dna methylation
- oxidative stress
- cell death
- genome wide
- multiple sclerosis
- resting state
- cerebral ischemia
- transcription factor