Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats
Characterization of weight loss and weight regain mechanisms after Roux-en-Y gastric bypass in rats
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DOI：
10.1152/ajpregu.00171.2007
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发表时间：
2007-10-01
影响因子：
2.8
通讯作者：
Meguid, Michael M.
中科院分区：
文献类型：
--
作者：
Guijarro, Ana;Suzuki, Susumu;Meguid, Michael M.
Roux-en-Y胃旁路术（RYGB）是治疗病态肥胖症最有效的方法，但其失败率接近20%。为了验证我们的假设，即结果取决于几种能量相关系统的差异修饰，我们在Sprague-Dawley饮食诱导的肥胖（DIO）大鼠中使用我们建立的RYGB模型来确定导致成功（RGYB-S）或失败（RYGB-F）RYGB的机制。将DIO大鼠随机分为RYGB组、假手术肥胖组和假手术肥胖配对喂养RYGB（PF）组。每天记录体重（BW）、热量摄入（CI）和粪便排出量（FO），持续90天，计算食物效率（FE），并测定形态学变化。研究了D-木糖和脂肪的吸收。记录葡萄糖刺激胃迷走神经传出神经放电频率。测定血浆中的肠道、脂肪和甲状腺激素。对骨骼肌线粒体呼吸复合物和能量相关下丘脑和脂肪肽、受体和酶的表达进行定量。失败率为25%。与肥胖大鼠相比，RYGB-S、RYGB-F和PF大鼠显示出快速的BW降低，随后在RYGB-S大鼠中出现持续的BW损失。RYGB-F和PF大鼠体重逐渐增加。RYGB-S大鼠中的BW损失不仅通过RYGB诱导的Cl降低和FO增加来实现，而且还通过交感神经系统激活来实现，所述交感神经系统激活由增加的肽YY、CRF和食欲素信号传导驱动，减少FE和能量储存，这通过与脂肪中线粒体解偶联蛋白-2的上调相关的脂肪量减少来证明。这些事件超越了旨在保存能量的对瘦素水平下降的补偿反应。
Roux-en-Y gastric bypass (RYGB) is the most effective therapy for morbid obesity, but it has a similar to 20% failure rate. To test our hypothesis that outcome depends on differential modifications of several energy-related systems, we used our established RYGB model in Sprague-Dawley diet-induced obese (DIO) rats to determine mechanisms contributing to successful (RGYB-S) or failed (RYGB-F) RYGB. DIO rats were randomized to RYGB, sham-operated Obese, and sham-operated obese pair-fed linked to RYGB (PF) groups. Body weight (BW), caloric intake (CI), and fecal output (FO) were recorded daily for 90 days, food efficiency (FE) was calculated, and morphological changes were determined. D-Xylose and fat absorption were studied. Glucose-stimulated vagal efferent nerve firing rates of stomach were recorded. Gut, adipose, and thyroid hormones were measured in plasma. Mitochondrial respiratory complexes in skeletal muscle and expression of energy-related hypothalamic and fat peptides, receptors, and enzymes were quantified. A 25% failure rate occurred. RYGB-S, RYGB-F, and PF rats showed rapid BW decrease vs. Obese rats, followed by sustained BW loss in RYGB-S rats. RYGB-F and PF rats gradually increased BW. BW loss in RYGB-S rats is achieved not only by RYGB-induced decreased Cl and increased FO, but also via sympathetic nervous system activation, driven by increased peptide YY, CRF, and orexin signaling, decreasing FE and energy storage, demonstrated by reduced fat mass associated with the upregulation of mitochondrial uncoupling protein-2 in fat. These events override the compensatory response to the drop in leptin levels aimed at conserving energy.