Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach.
Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach.
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DOI：
10.1016/j.mce.2009.12.023
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发表时间：
2010-04-12
影响因子：
4.1
通讯作者：
Luque RM
中科院分区：
文献类型：
--
作者：
Gahete MD;Córdoba-Chacón J;Salvatori R;Castaño JP;Kineman RD;Luque RM
胃饥饿素是调节食物摄入、身体组成、生长和能量平衡等生理过程的内分泌环节。胃饥饿素是已知的唯一经过辛烷酰化的肽。介导这一过程的酶，胃饥饿素o -酰基转移酶（GOAT），在胃肠道（GI；循环胃饥饿素的主要来源）和其他组织中表达。本研究表明，在禁食和饮食诱导的肥胖小鼠中，胃GOAT mRNA水平与循环酰化胃饥饿素水平相关。此外，研究发现，GOAT在垂体和下丘脑（ghrelin作用的两个靶组织）均有表达，并根据代谢状态进行调节。以垂体原代细胞培养为模型系统研究山羊的表达调控，我们发现乙酰化胃饥饿素增加了山羊的表达，而去乙酰化胃饥饿素没有增加山羊的表达。此外，生长激素释放激素（GHRH）和瘦素（leptin）表达升高，而生长抑素（SST）表达降低。这些结果的生理学相关性得到了以下观察结果的支持：缺乏GHRH、SST和leptin的小鼠垂体GOAT表达与体外处理相应肽后的变化相反。因此，这些激素直接参与垂体GOAT的调节似乎是合理的。有趣的是，在所研究的所有模型中，垂体GOAT的表达与ghrelin的优势剪接变体（In2-ghrelin）的表达变化相似，因此该转录物可能是垂体GOAT的主要底物。总的来说，这些观察结果支持这样的观点，即胃肠道不是饥饿素酰化的唯一来源，但事实上，局部产生的去酰化的饥饿素可以通过局部活性的山羊在靶组织内转化为酰化的饥饿素，从而介导其组织特异性作用。
Ghrelin acts as an endocrine link connecting physiological processes regulating food intake, body composition, growth, and energy balance. Ghrelin is the only peptide known to undergo octanoylation. The enzyme mediating this process, ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI; primary source of circulating ghrelin) as well as other tissues. The present study demonstrates that stomach GOAT mRNA levels correlate with circulating acylated-ghrelin levels in fasted and diet-induced obese mice. In addition, GOAT was found to be expressed in both the pituitary and hypothalamus (two target tissues of ghrelin’s actions), and regulated in response to metabolic status. Using primary pituitary cell cultures as a model system to study the regulation of GOAT expression, we found that acylated-ghrelin, but not desacyl-ghrelin, increased GOAT expression. In addition, growth-hormone-releasing hormone (GHRH) and leptin increased, while somatostatin (SST) decreased GOAT expression. The physiologic relevance of these later results is supported by the observation that pituitary GOAT expression in mice lacking GHRH, SST and leptin showed opposite changes to those observed after in vitro treatment with the corresponding peptides. Therefore, it seems plausible that these hormones directly contribute to the regulation of pituitary GOAT. Interestingly, in all the models studied, pituitary GOAT expression paralleled changes in the expression of a dominant spliced-variant of ghrelin (In2-ghrelin) and therefore this transcript may be a primary substrate for pituitary GOAT. Collectively, these observations support the notion that the GI tract is not the only source of acylated-ghrelin, but in fact locally-produced des-acylated-ghrelin could be converted to acylated-ghrelin within target tissues by locally active GOAT, to mediate its tissue-specific effects.
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影响因子：
82.9
作者：
通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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