Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.
Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.
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DOI：
10.1371/journal.pone.0030672
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
De Salles AA
中科院分区：
文献类型：
--
作者：
Melega WP;Lacan G;Gorgulho AA;Behnke EJ;De Salles AA
先前对食欲调节网络的研究，主要是在啮齿动物中，已经确定了对下丘脑腹内侧（VMH）的定向电刺激可以改变食物摄入模式和代谢稳态。考虑将这种方法用于严重暴饮暴食症和病态肥胖患者的体重调节，可以通过建模程序和评估终点来进一步推进，这些终点可以提供关于疗效和安全性的临床前数据。在这项研究中，我们采用了人类深部脑刺激（DBS）的立体定向方法和仪器，在大型动物模型中证明了VMH-DBS对体重增加的调节。使用雌性Göttingen迷你猪是因为它们的饮食习惯、生理特征和大脑结构与灵长类动物相似。此外，这些动物在额外的喂养方案下变得肥胖。首先将DBS电极植入动物的双侧VMH (n = 8)，然后在手术后1个月保持限制饮食。在接下来的2个月里，所有动物的每日食物量增加一倍，以产生与额外卡路里摄入相关的肥胖，其中一半动物（n = 4）同时接受连续的低频（50 Hz） VMH-DBS。手术后或DBS期间未观察到不良的运动或行为影响。在这2个月的DBS期间，所有动物每天消耗的食物量增加了一倍。然而，接受VMH-DBS的动物的累积体重增加（6.1±0.4 kg；平均值±SEM）低于未接受VMH-DBS刺激的动物（9.4±1.3 kg; p<0.05），提示与dbs相关的代谢率增加。在猪肥胖模型中的这些结果证明了低频VMH-DBS应用作为调节体重的潜在临床策略的有效性和行为安全性。
Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.
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影响因子：
120.7
作者：
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通讯作者：
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Sorensen, Jens-Christian
影响因子：
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作者：
Butson, CR;Maks, CB;McIntyre, CC
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McIntyre, CC