Insulin and leptin combine additively to reduce food intake and body weight in rats
Insulin and leptin combine additively to reduce food intake and body weight in rats
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DOI：
10.1210/en.143.6.2449
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发表时间：
2002-06-01
期刊：
影响因子：
4.8
通讯作者：
Woods, SC
中科院分区：
文献类型：
--
作者：
Air, EL;Benoit, SC;Woods, SC
瘦素和胰岛素是调节食物摄入和体重的不同肥胖信号。由于最近的证据表明，每种物质的中枢分解代谢作用都是由下丘脑黑皮质素系统介导的，因此我们测试了瘦素和胰岛素在大脑内相互作用的假设，无论是相加还是协同，以抑制食物摄入并减轻体重。采用受试者内部设计，我们将瘦素和胰岛素以多种剂量共同施用到 3,4 脑室 (i.c.v.)，并将组合效果与单独施用每种肽后发生的效果进行比较。数据表明，瘦素和胰岛素在最初的几个小时内相互作用，以亚加性的方式调节食物摄入和体重。也就是说，瘦素和胰岛素的组合减少食物摄入和体重的能力小于它们独立作用的总和所预测的能力。然而，在 24 小时内，组合剂量符合严格相加模型。因此，这些数据意味着瘦素和胰岛素在食物摄入和体重的急性调节中所利用的功能性细胞内途径或神经元回路存在冗余，并且它们进一步意味着随着时间的推移，冗余会消失。
Leptin and insulin are distinct adiposity signals that regulate food intake and body weight. Because recent evidence suggests that the central catabolic action of each is mediated by the hypothalamic melanocortin system, we tested the hypothesis that leptin and insulin interact within the brain, either additively or synergistically, to suppress food intake and reduce body weight. Using a within subjects design, we co-administered leptin and insulin into the 3,4 cerebral ventricle (i.c.v.) over a wide range of doses, and compared the combined effects to what occurred following the administration of each peptide alone. The data suggest that leptin and insulin interact sub-additively to regulate food intake and body weight over the first few hours. That is, the ability of combinations of leptin and insulin to reduce food intake and body weight was less than what would be predicted by the sum of their independent actions. Over 24 hours, however, the combined doses fit a strictly additive model. These data therefore imply a redundancy in the functional intracellular pathways or neuronal circuits that leptin and insulin utilize in the acute regulation of food intake and body weight, and they further imply that over time, the redundancy dissipates.