Huang Linfang, Toyoshima Megumi, Asakawa Akihiro, Inoue Kayoko, Harada Kouji, Kinoshita Tomomi, Chen Shilin, Koizumi Akio
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 1000193, China.
Pharmacol Biochem Behav. 2009 Mar;92(1):1-5. doi: 10.1016/j.pbb.2008.10.003. Epub 2008 Nov 1.
O,O,S-Trimethylphosphorothioate (OOS-TMP) has been shown to induce hypophagia and hypopraxia. Recent studies suggest that OOS-TMP-induced anorexia is partly mediated by its effect on the central nervous system. In this study, we examined the profiles of N-acylethanolamines (NEAs), including five amide-linked compounds, in the gastrointestinal system in C57BL/6J (B6) mice. The present results shown an orexigenic profile of the levels of NEAs with downregulation of the anorectic lipid, N-stearoylethanolamine (SEA), upregulation of the orexigenic lipid, 2-arachidonoyl glycerol (2-AG), at 2 h and upregulation of 2-AG at 24 h albeit with significant anorexia. However, the data indicated that the high level of 2-AG may be responsible for the hypopraxia. We next explored whether OOS-TMP may affect two models of hyperphagia and hyperglycemia, ins2(+/Akita) B6 (Akita) and B6-lepr(db)/lepr(db) mice (db/db). We identified potential anorexigenic effects in B6, Akita and db/db mice. Moreover, OOS-TMP was found to reduce blood glucose in Akita mice but not in db/db mice. Collectively, these findings suggest that N-acylethanolamines are not involved in the hypophagia but rather hypopraxia, and may play multiple physiological roles in this process. OOS-TMP might be a promising candidate for anti-obesity and anti-diabetic drug development.
硫代磷酸O,O,S-三甲基酯（OOS-TMP）已被证明可诱导食欲减退和运动不能。最近的研究表明，OOS-TMP诱导的厌食症部分是由其对中枢神经系统的作用介导的。在本研究中，我们检测了C57BL/6J（B6）小鼠胃肠道系统中N-酰基乙醇胺（NEA）的概况，包括五种酰胺连接的化合物。目前的结果显示，NEA水平呈现促食欲特征，厌食性脂质N-硬脂酰乙醇胺（SEA）下调，促食欲脂质2-花生四烯酸甘油酯（2-AG）在2小时时上调，在24小时时2-AG也上调，尽管存在明显的厌食症。然而，数据表明高水平的2-AG可能是运动不能的原因。接下来，我们探究了OOS-TMP是否可能影响两种食欲亢进和高血糖模型，即ins2(+/Akita) B6（Akita）和B6-lepr(db)/lepr(db)小鼠（db/db）。我们在B6、Akita和db/db小鼠中发现了潜在的厌食作用。此外，发现OOS-TMP可降低Akita小鼠的血糖，但对db/db小鼠无效。总的来说，这些发现表明N-酰基乙醇胺不参与食欲减退，而是参与运动不能，并且可能在这个过程中发挥多种生理作用。OOS-TMP可能是抗肥胖和抗糖尿病药物开发的一个有前途的候选药物。
