Objective

Roux-en-Y gastric surgery (RYGB) promotes a rapid and sustained weight loss and amelioration of glucose control in obese patients. A high number of molecular hypotheses were previously tested using duodenal-jejunal bypass (DJB) performed in various genetic models of mice with knockouts for various hormones or receptors. The data were globally negative or inconsistent. Therefore, the mechanisms remained elusive. Intestinal gluconeogenesis is a gut function that has been suggested to contribute to the metabolic benefits of RYGB in obese patients.

Methods

We studied the effects of DJB on body weight and glucose control in obese mice fed a high fat-high sucrose diet. Wild type mice and mice with a genetic suppression of intestinal gluconeogenesis were studied in parallel using glucose- and insulin-tolerance tests. Fecal losses, including excretion of lipids, were studied from the feces recovered in metabolic cages.

Results

DJB induced a dramatic decrease in body weight and improvement in glucose control (glucose- and insulin-tolerance) in obese wild type mice fed a high calorie diet, for 25 days after the surgery. The DJB-induced decrease in food intake was transient and resumed to normal in 7–8 days, suggesting that decreased food intake could not account for the benefits. Total fecal losses were about 5 times and lipid losses 7 times higher in DJB-mice than in control (sham-operated and pair-fed) mice, and could account for the weight loss of mice. The results were comparable in mice with suppression of intestinal gluconeogenesis. There was no effect of DJB on food intake, body weight or fecal loss in lean mice fed a normal chow diet.

Conclusions

DJB in obese mice fed a high calorie diet promotes dramatic fecal loss, which could account for the dramatic weight loss and metabolic benefits observed. This could dominate the effects of the mouse genotype/phenotype. Thus, fecal energy loss should be considered as an essential process contributing to the metabolic benefits of DJB in obese mice.

中文翻译：

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小鼠胃旁路手术的代谢益处：粪便流失的作用。

客观的

Roux-en-Y胃外科手术（RYGB）可促进肥胖患者快速且持续的体重减轻和血糖控制的改善。先前使用十二指肠-空肠旁路术（DJB）在具有各种激素或受体基因敲除小鼠的各种遗传模型中进行了测试，从而测试了许多分子假设。数据在整体上是负面的或不一致的。因此，该机制仍然难以捉摸。肠道糖异生是一种肠道功能，已被认为有助于肥胖患者RYGB的代谢益处。

方法

我们研究了DJB对高脂高蔗糖饮食喂养的肥胖小鼠体重和血糖控制的影响。使用葡萄糖耐量试验和胰岛素耐量试验平行研究了野生型小鼠和对肠道糖异生具有遗传抑制作用的小鼠。从代谢笼中回收的粪便研究了粪便流失，包括脂质的排泄。

结果

在手术后的25天里，DJB诱导了高热量饮食的肥胖野生型小鼠体重的显着降低和葡萄糖控制（葡萄糖和胰岛素耐受性）的改善。DJB引起的食物摄入量的减少是短暂的，并在7-8天后恢复正常，这表明食物摄入量的减少无法说明其益处。DJB小鼠的总粪便损失约为对照小鼠（假手术和成对喂养的小鼠）的5倍，脂质损失高7倍，可以解释小鼠的体重减轻。在抑制肠道糖异生的小鼠中，该结果是可比的。DJB对普通饮食喂养的瘦小鼠的食物摄入，体重或粪便损失没有影响。

结论

饲喂高卡路里饮食的肥胖小鼠中的DJB会导致粪便大量流失，这可以解释观察到的体重减轻和代谢益处。这可以主导小鼠基因型/表型的作用。因此，粪便能量损失应被认为是导致肥胖小鼠DJB代谢益处的重要过程。