Peripheral oxyntomodulin reduces food intake and body weight gain in rats
Peripheral oxyntomodulin reduces food intake and body weight gain in rats
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DOI：
10.1210/en.2003-1338
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发表时间：
2004-06-01
期刊：
影响因子：
4.8
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
Dakin, CL;Small, CJ;Bloom, SR
胃泌酸调节素（OXM）是餐后从胃肠道粘膜细胞释放的循环肠道激素。给大鼠脑室内注射，它会抑制食物摄入并促进体重减轻。在这里，我们报告，外周（IP）给药的OXM剂量依赖性抑制快速诱导和暗相的食物摄入，而不延迟胃排空。外周OXM给药也抑制空腹血浆ghrelin。此外，在弓状核（ARC）中，c-fos免疫反应性（神经元14激活的标记物）显著增加。直接注射到ARC中的OXM引起禁食后再进食的有效和持续减少。先前ARC内给予胰高血糖素样肽-1（GLP-1）受体拮抗剂exendin（9-39）可阻断ip OXM的厌食作用，表明缺乏完整血脑屏障的ARC可能是循环OXM的潜在作用部位。然而，ip GLP-1的作用未被先前ARC内给予毒蜥外泌肽阻断（9-39），表明可能存在不同的OXM和GLP-1途径。七天的ip给药OXM引起体重增加率和肥胖率的降低。循环OXM可能在调节食物摄入和体重中起作用。
Oxyntomodulin (OXM) is a circulating gut hormone released post prandially from cells of the gastrointestinal mucosa. Given intracerebroventricularly to rats, it inhibits food intake and promotes weight loss. Here we report that peripheral (ip) administration of OXM dose-dependently inhibited both fast-induced and dark-phase food intake without delaying gastric emptying. Peripheral OXM administration also inhibited fasting plasma ghrelin. In addition, there was a significant increase in c-fos immunoreactivity, a marker of neuronal 14 activation, in the arcuate nucleus (ARC). OXM injected directly into the ARC caused a potent and sustained reduction in refeeding after a fast. The anorectic actions of ip OXM were blocked by prior intra-ARC administration of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin(9-39), suggesting that the ARC, lacking a complete blood-brain barrier, could be a potential site of action for circulating OXM. The actions of ip GLP-1, however, were not blocked by prior intra-ARC administration of exendin(9-39), indicating the potential existence of different OXM and GLP-1 pathways. Seven-day ip administration of OXM caused a reduction in the rate of body weight gain and adiposity. Circulating OXM may have a role in the regulation of food intake and body weight.