Obesity, Metabolism & Nutritional Institute and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R985-93. doi: 10.1152/ajpregu.00262.2012. Epub 2012 Sep 12.
Roux-en-Y gastric bypass (RYGB) in rodent models reduces food intake (FI), increases resting energy expenditure (EE), and improves glycemic control. We have shown that mimicking the duodenal component of RYGB by implantation of a 10-cm endoluminal sleeve device (ELS-10) induces weight loss and improves glycemic control in diet-induced obese (DIO) rats. We sought to determine the mechanisms and structural requirements of these effects. We examined the effects of ELS-10 devices implanted in male DIO rats on body weight, food intake (FI), meal patterns, total and resting EE, and multiple parameters of glucose homeostasis, comparing them with sham-operated (SO) rats and with SO rats weight matched to the ELS-10-treated group. To determine the extent of duodenal exclusion required to influence metabolic outcomes, we compared the effects of implanting 10-, 4-, or 1-cm ELS devices. ELS-10 rats exhibited 13% higher total and 9% higher resting EE than SO controls. ELS-10 rats also exhibited enhanced postprandial GLP-1 secretion and improved glucose tolerance and insulin sensitivity out of proportion to the effects of weight loss alone. Implantation of 4- or 1-cm ELS devices had no effect on EE and limited effects on glucose homeostasis. Complete duodenal exclusion with ELS-10 induces weight loss by decreasing FI and increasing EE and improves glycemic control through weight loss-independent mechanisms. Thus signals originating in the proximal small intestine appear to exert a direct influence on the physiological regulation of EE and glucose homeostasis. Their selective manipulation could provide effective new therapies for obesity and diabetes that mimic the benefits of RYGB.
胃旁路手术（RYGB）在啮齿动物模型中可减少食物摄入量（FI），增加静息能量消耗（EE），并改善血糖控制。我们已经表明，通过植入 10cm 腔内袖套装置（ELS-10）模拟 RYGB 的十二指肠部分，可诱导肥胖症（DIO）大鼠减肥并改善血糖控制。我们试图确定这些效果的机制和结构要求。我们检查了植入雄性 DIO 大鼠体内的 ELS-10 装置对体重、食物摄入量（FI）、进餐模式、总静息 EE 和多种血糖稳态参数的影响，并将其与假手术（SO）大鼠和体重与 ELS-10 治疗组匹配的 SO 大鼠进行了比较。为了确定影响代谢结果所需的十二指肠排除程度，我们比较了植入 10cm、4cm 或 1cm ELS 装置的效果。ELS-10 大鼠的总 EE 和静息 EE 分别比 SO 对照组高 13%和 9%。ELS-10 大鼠还表现出餐后 GLP-1 分泌增强，以及葡萄糖耐量和胰岛素敏感性改善，与单独减肥的效果不成比例。植入 4cm 或 1cm ELS 装置对 EE 没有影响，对葡萄糖稳态的影响有限。ELS-10 完全排除十二指肠可通过减少 FI 和增加 EE 来减轻体重，并通过与体重减轻无关的机制改善血糖控制。因此，起源于近端小肠的信号似乎对 EE 和葡萄糖稳态的生理调节直接产生影响。对这些信号的选择性操作可能为肥胖症和糖尿病提供有效的新疗法，这些疗法模仿 RYGB 的益处。
