Mondal Muhtashan S, Toshinai Koji, Ueno Hiroaki, Koshinaka Keiichi, Nakazato Masamitsu
Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
J Endocrinol. 2008 Aug;198(2):339-46. doi: 10.1677/JOE-08-0082. Epub 2008 May 14.
Obestatin is a 23-amino acid peptide, initially isolated from rat stomach as an endogenous ligand for the orphan G-protein-coupled receptor. Obestatin is derived from proteolytic cleavage of a 117-amino acid 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 on 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 in 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 on feeding behavior.
肥胖抑制素是一种由23个氨基酸组成的肽，最初作为孤儿G蛋白偶联受体的内源性配体从大鼠胃中分离出来。肥胖抑制素由117个氨基酸的前体——前proghrelin经蛋白水解切割产生。胃饥饿素可增加食物摄入量、体重并加快胃排空，而肥胖抑制素则具有相反的作用。在本研究中，我们对大鼠和人类胃中的肥胖抑制素进行了表征，并研究了该肽对摄食行为的影响。使用反相高效液相色谱法结合针对大鼠和人类肥胖抑制素的放射免疫分析法，我们在胃底中检测到与胃饥饿素相比含量极少的肥胖抑制素。在大鼠和人类胃底中，肥胖抑制素与胃饥饿素的比例分别为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%，而在大鼠血浆中则无法检测到。正常受试者进食后血浆胃饥饿素浓度降低，而肥胖抑制素浓度没有变化。当经中枢或外周给药时，肥胖抑制素在自由进食或禁食的啮齿动物中均未抑制食物摄入。给予肥胖抑制素并未拮抗胃饥饿素诱导的进食。这些发现表明，与胃饥饿素相比，肥胖抑制素在大鼠和人类中的含量都非常低，并且对摄食行为没有急性影响。
