Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.
Obesity, POMC, and POMC-processing Enzymes: Surprising Results From Animal Models.
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DOI：
10.1210/endocr/bqab155
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发表时间：
2021-12-01
期刊：
影响因子：
4.8
通讯作者：
Fricker LD
中科院分区：
文献类型：
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作者：
Lindberg I;Fricker LD
源自阿片黑皮素原 (POMC) 的肽是成熟的神经肽和肽激素，具有多种功能，包括调节体重。在人类和某些动物中，这些肽包括 α- 和 β- 黑素细胞刺激激素 (MSH)。在某些啮齿类动物中，由于裂解位点的变化，POMC 不会产生 β-MSH。将 POMC 转化为 MSH 的酶包括激素原转化酶 (PC)、羧肽酶 (CP) 和肽基-α-酰胺化单加氧酶 (PAM)。 PC1/3 或羧肽酶 E (CPE) 失活突变的人和小鼠肥胖，这被认为是由于 POMC 加工成 MSH 的过程有缺陷造成的。然而，最近的研究表明，POMC 表达细胞中 PC1/3 或 CPE 的选择性缺失不会导致肥胖。这些发现表明 POMC 处理缺陷不能单独解释在全球 PC1/3 或 CPE 突变体中观察到的肥胖现象。我们认为，缺乏 PC1/3 或 CPE 活性的动物的肥胖至少部分取决于大脑和/或外周非 POMC 表达细胞中肽的加工缺陷。遗传背景也可能导致肥胖的表现。
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.