Characterization of obestatin in rat and human stomach and plasma, and its lack of acute effect on feeding behavior in rodents
Characterization of obestatin in rat and human stomach and plasma, and its lack of acute effect on feeding behavior in rodents
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DOI：
10.1677/joe-08-0082
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发表时间：
2008-08-01
影响因子：
4
通讯作者：
Nakazato, Masamitsu
中科院分区：
文献类型：
--
作者：
Mondal, Muhtashan S.;Toshinai, Koji;Nakazato, Masamitsu
Obestatin是一种含有23个氨基酸的肽，最初从大鼠胃中分离出来，作为孤儿g蛋白偶联受体的内源性配体。Obestatin是由一个含有117个氨基酸的前体pre - proghrelin的蛋白水解裂解而来。胃促生长素增加食物摄入量、体重和胃排空，而肥胖抑制素则有相反的效果。在本研究中，我们在大鼠和人的胃中对肥胖抑制素进行了表征，并研究了该肽对油脂摄食行为的影响。利用反相高效液相色谱联用大鼠和人肥胖抑制素特异性RIAs，与胃饥饿素相比，我们在胃底检测到极少量的肥胖抑制素。在大鼠和人胃底中，肥胖抑制素与胃饥饿素的比值分别为0.0039和1.94%。在人类中，血浆肥胖抑制素占胃饥饿素浓度的5.21%，而在大鼠血浆中检测不到。正常受试者餐后血浆胃饥饿素浓度下降，而肥胖抑制素浓度没有变化。无论是集中给药还是外周给药，肥胖抑制素都不能抑制自由喂养或禁食啮齿动物的食物摄入。给予肥胖抑制素对胃饥饿素诱导的喂养没有拮抗作用。这些发现表明，与饥饿素相比，肥胖抑制素在大鼠和人体内的含量都很低，并且对油脂摄食行为没有急性影响。
Obestatin is a 23-amino acid peptide, initially isolated from rat stomach as all endogenous ligand for the orphan G-protein-coupled receptor. Obestatin is derived from proteolytic cleavage of a 117-aminoacid precursor, preproghrelin. Ghrelin increases food intake, body weight, and gastric emptying, whereas obestatin has the opposite effects. In this study, we characterized obestatin in both rat and human stomach, and investigated the peptide's effect oil feeding behavior. Using reversed-phase high-performance liquid chromatography coupled with RIAs specific for rat and human obestatin, we detected a very small amount of obestatin, compared with ghrelin, in the gastric fundi. The ratios of obestatin to ghrelin are 0.0039 and 1.94% respectively in the rat and human gastric fundi. In humans, plasma obestatin accounted for 5.21% of the ghrelin concentration, whereas it was undetectable in rat plasma. Plasma ghrelin concentration decreased after a meal it) normal subjects, whereas obestatin concentration did not change. When administered centrally or peripherally, obestatin did not suppress food intake in either free-feeding or fasted rodents. Administration of obestatin did not antagonize ghrelin-induced feeding. These findings indicate that obestatin is present at very low levels compared with ghrelin in both rat and human, and has no acute effect oil feeding behavior.