Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight.
Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight.
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DOI：
10.1016/j.peptides.2009.11.019
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发表时间：
2010-02
期刊：
影响因子：
3
通讯作者：
Taché Y
中科院分区：
文献类型：
--
作者：
Stengel A;Goebel M;Wang L;Taché Y
肠粘膜内分泌细胞释放的许多肽很早就被确定参与食物摄入的生理调节，当营养物质通过肠道时，在终止食物摄入方面发挥着重要作用。最近，胃泌酸粘膜 X/A 样内分泌细胞释放的肽被认为是调节摄食和能量消耗的另一个关键因素。胃 X/A 样细胞释放辛酰化肽 ghrelin，这是唯一已知的外周产生的激素，通过与生长激素促分泌素 1a 受体 (GHS-R1a) 相互作用刺激食物摄入。此外，循环中存在的非辛酰化（去酰基）生长素释放肽的水平高于生长素释放肽，目前被认为是潜在的食物摄入调节剂，通过对抗生长素释放肽的独立于 GHS-R1a 的作用，尽管其功能意义仍有待确定。肥胖素（Obestatin）是一种与生长素释放肽相关的肽，最初被报道为生长素释放肽促食欲作用的抑制食欲调节剂。但随后的报道并未支持这一说法。有趣的是最近发现的 nesfatin-1，这是一种源自 nucleobindin2 基因的肽，在胃部 X/A 样细胞的不同囊泡中显着表达，与 ghrelin 不同。循环中的nesfatin-1水平随代谢状态而变化，外周或中枢注射可抑制啮齿类动物的暗期进食。总体而言，这些数据表明胃的 X/A 样细胞通过表达促食欲肽 ghrelin 以及去酰基 ghrelin 和 nesfatin-1 在食物摄入调节中发挥重要作用，能够在外源注射后减少食物摄入，尽管它们的作用机制和功能意义仍有待确定。
Numerous peptides released from endocrine cells in the intestinal mucosa were established early on to be involved in the physiological regulation of food intake with a prominent role in termination of food ingestion when nutrients pass along the intestinal tract. Recently, peptides released from X/A-like endocrine cells of the gastric oxyntic mucosa were recognized as additional key players in the regulation of feeding and energy expenditure. Gastric X/A-like cells release the octanoylated peptide, ghrelin, the only known peripherally produced hormone stimulating food intake through interaction with growth hormone secretagogue 1a receptor (GHS-R1a). Additionally, non-octanoylated (des-acyl) ghrelin present in the circulation at higher levels than ghrelin is currently discussed as potential modulator of food intake by opposing ghrelin’s action independent from GHS-R1a although the functional significance remains to be established. Obestatin, a ghrelin-associated peptide was initially reported as anorexigenic modulator of ghrelin’s orexigenic action. However, subsequent reports did not support this contention. Interesting is the recent identification of nesfatin-1, a peptide derived from the nucleobindin2 gene prominently expressed in the stomach in gastric X/A-like cells in different vesicles than ghrelin. Circulating nesfatin-1 levels vary with metabolic state and peripheral or central injection inhibits dark phase feeding in rodents. Overall, these data point to an important role of X/A-like cells of the stomach in food intake regulation through the expression of the orexigenic peptide ghrelin along with des-acyl ghrelin and nesfatin-1 capable of reducing food intake upon exogenous injection although their mechanisms of action and functional significance remain to be established.
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