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首页> 外文期刊>American Journal of Physiology >Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract.
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Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract.

机译：空腹和瘦素对弓形核和孤立道核中proopiomelanocortin肽的不同作用。

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The alpha-melanocyte-stimulating hormone (alpha-MSH), derived from proopiomelanocortin (POMC), is generated by a posttranslational processing mechanism involving the prohormone convertases (PCs) PC1/3 and PC2. In the brain, alpha-MSH is produced in the arcuate nucleus (ARC) of the hypothalamus and in the nucleus of the solitary tract (NTS) of the medulla. This peptide is key in controlling energy balance, as judged by changes observed at transcriptional level. However, little information is available regarding the biosynthesis of the precursor POMC and the production of its processed peptides during feeding, fasting, and fasting plus leptin in the ARC compared with the NTS in conjunction with the PC activity. In this study we found that, in the ARC, pomc mRNA, POMC-derived peptides, and PC1/3 all decreased during fasting, and administration of leptin reversed these effects. In contrast, in the NTS, where there is a large amount of a 28.1-kDa peptide similar in size to POMC, the 28.1-kDa peptide and other POMC-derived peptides, including alpha-MSH, were further accumulated in fasting conditions, whereas pomc mRNA decreased. These changes were not reversed by leptin. We also observed that, during fasting, PC2 levels decreased in the NTS. These data suggest that, in the NTS, fasting induced changes in POMC biosynthesis, and processing is independent of leptin. These observations indicate that changes in energy status affect POMC in the brain in a tissue-specific manner. This represents a novel aspect in the regulation of energy balance and may have implications in the pathophysiology of obesity.
机译：源自proopiomelanocortin（POMC）的α-黑素细胞刺激激素（alpha-MSH）是由涉及激素原转化酶（PCs）PC1 / 3和PC2的翻译后加工机制产生的。在大脑中，α-MSH在下丘脑的弓形核（ARC）和延髓的孤立道（NTS）的核中产生。根据在转录水平观察到的变化判断，该肽是控制能量平衡的关键。但是，与NTS结合PC活性相比，关于前体POMC的生物合成及其在进食，禁食和禁食中加瘦素过程中的前体POMC的生物合成及其产生的肽的信息很少。在这项研究中，我们发现，在禁食期间，ARC中的pomc mRNA，POMC衍生的肽和PC1 / 3均下降，而瘦素的给药逆转了这些作用。相反，在NTS中，存在大量大小类似于POMC的28.1-kDa肽，在禁食条件下，28.1-kDa肽和其他POMC衍生的肽（包括α-MSH）被进一步积累，而pomc mRNA降低。瘦素不能逆转这些变化。我们还观察到，禁食期间，NTS中的PC2水平下降。这些数据表明，在NTS中，禁食引起POMC生物合成的变化，并且加工过程与瘦素无关。这些观察表明，能量状态的变化以组织特异性的方式影响大脑中的POMC。这代表了能量平衡调节的一个新方面，可能对肥胖症的病理生理学有影响。

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