Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents
Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents
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DOI：
10.1530/joe-19-0102
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Nakazato, Masamitsu
中科院分区：
文献类型：
--
作者：
Islam, Md Nurul;Mita, Yuichiro;Nakazato, Masamitsu
Ghrelin是一种胃源性肽，可促进摄食和生长激素（GH）分泌。最近的一项研究确定了肝脏表达的抗菌肽2（LEAP 2）作为生长激素释放肽诱导的GH分泌的内源性抑制剂，但LEAP 2在大脑中的作用仍然未知。在这项研究中，我们表明，脑室内（i.c.v.）对大鼠施用LEAP 2抑制了中枢生长素释放肽功能，包括下丘脑核中的Fos表达、食物摄取的促进、血糖升高和体温降低。LEAP 2不抑制神经肽Y（NPY）诱导的食物摄入或去酰基ghrelin诱导的体温降低，表明LEAP 2的抑制作用是特异性的GHSR。血浆LEAP 2水平根据喂养状态而变化，并且似乎依赖于肝脏Leap 2表达。此外，ghrelin通过激活AMPK抑制肝脏Leap 2的表达。总而言之，这些结果表明LEAP 2抑制中枢生长激素释放肽功能以及肝脏和胃之间的串扰。
Ghrelin, a stomach-derived peptide, promotes feeding and growth hormone (GH) secretion. A recent study identified liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inhibitor of ghrelin-induced GH secretion, but the effect of LEAP2 in the brain remained unknown. In this study, we showed that intracerebroventricular (i.c.v.) administration of LEAP2 to rats suppressed central ghrelin functions including Fos expression in the hypothalamic nuclei, promotion of food intake, blood glucose elevation, and body temperature reduction. LEAP2 did not inhibit neuropeptide Y (NPY)-induced food intake or des-acyl ghrelin-induced reduction in body temperature, indicating that the inhibitory effects of LEAP2 were specific for GHSR. Plasma LEAP2 levels varied according to feeding status and seemed to be dependent on the hepatic Leap2 expression. Furthermore, ghrelin suppressed the expression of hepatic Leap2 via AMPK activation. Together, these results reveal that LEAP2 inhibits central ghrelin functions and crosstalk between liver and stomach.