Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling.

Effect of vertical sleeve gastrectomy on alcohol consumption and preferences in dietary obese rats and mice: A plausible role for altered ghrelin signaling.
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DOI:
10.1016/j.brainresbull.2017.08.004
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发表时间:
2018-04
影响因子:
3.8
通讯作者:
Hajnal A
Hajnal A
中科院分区:
医学3区
文献类型:
--
作者:
Orellana ER;Jamis C;Horvath N;Hajnal A

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垂直袖状胃切除术(VSG)和Roux-en-Y胃绕道术(RYGB)是治疗肥胖和代谢紊乱最常见的手术选择。虽然 RYGB 可能会导致更大、更持久的体重减轻,但最近对大鼠进行的临床和临床前研究引起了人们的担忧,即 RYGB 手术可能会增加酒精使用障碍 (AUD) 的风险。相比之下,最近的临床报告表明,VSG 后发生 AUD 的风险较低,尽管尚未进行临床前研究证实这一点。因此,本研究试图使用类似于之前 RYGB 动物研究中使用的方案来确定 VSG 对啮齿动物模型中乙醇摄入和偏好的影响。雄性 Sprague Dawley 大鼠和雄性 C57B6 小鼠通过高脂肪饮食(60% kcal 来自脂肪)变得肥胖,并接受 VSG 或不接受手术(对照)。然后,所有动物都被给予浓度逐渐增加的乙醇(2%、4%、6% 和 8%),每次持续几天。与对照组相比,VSG 大鼠消耗的 2%、6% 和 8% 乙醇显着减少,并且对 6% 和 8% 乙醇的偏好明显低于水。 VSG 小鼠还表现出摄入量减少以及对 6% 和 8% 乙醇溶液的偏好。强制戒酒两周后,重新引入 8% 乙醇,VSG 大鼠和小鼠继续表现出消耗量减少和对乙醇的偏好减弱。关于潜在机制,我们假设 VSG 手术中去除胃中产生生长素释放肽的部分可能是观察到的乙醇偏好减少的一个原因。为了测试生长素释放肽受体的功能变化,在使用乙醇之前,对 VSG 和对照大鼠进行酰基生长素释放肽(2.5 nmol 和 5 nmol)的腹腔注射。两种生长素释放肽浓度均未导致 VSG 或对照受试者的 8% 乙醇消耗量显着增加。接下来,给大鼠腹腔注射生长素释放肽受体拮抗剂 JMV(2.5 毫克/千克体重)。该剂量使 VSG 组的乙醇消耗量显着减少 8%,但对对照组的乙醇摄入量没有影响。虽然 ghrelin 注射无法提供信息,但对阈下剂量的 ghrelin 受体拮抗剂的敏感性增加可能表明 VSG 后 ghrelin 信号传导减弱。总体而言,这些研究结果表明,对 AUD 敏感性增加的肥胖患者可能会受益于接受 VSG 而不是 RYGB 手术,并且 ghrelin 信号的变化(至少在一定程度上)可能在两种最常用的减肥手术之间的 AUD 风险差异中发挥作用。
Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most common surgical options for the treatment of obesity and metabolic disorder. Whereas RYGB may result in greater and more durable weight loss, recent clinical and pre-clinical studies in rats have raised concerns that RYGB surgery may increase risk for alcohol use disorder (AUD). In contrast, recent clinical reports suggest a lesser risk for AUD following VSG, although no preclinical studies have been done to confirm that. Therefore, the present study sought to determine the effects of VSG on ethanol intake and preferences in rodent models using protocols similar to those previously used in animal studies for RYGB. Male Sprague Dawley rats and male C57B6 mice were made obese on a high fat diet (60% kcal from fat) and received VSG or no surgery (controls). All animals then were given access to increasing concentrations of ethanol (2%, 4%, 6%, and 8%), presented for few days each. Compared to controls, VSG rats consumed significantly less of 2, 6 and 8% ethanol and showed significantly reduced preferences to 6 and 8% ethanol over water. VSG mice also displayed reduced intake and preference for 6 and 8% ethanol solutions. After a two-week period of forced abstinence, 8% ethanol was reintroduced and the VSG rats and mice continued to exhibit reduced consumption and less preference for ethanol. Regarding the underlying mechanism, we hypothesized that the removal of the ghrelin producing part of the stomach in the VSG surgery is a possible contributor to the observed reduced ethanol preference. To test for functional changes at the ghrelin receptors, the VSG and control rats were given IP injections of acyl-ghrelin (2.5 nmol and 5 nmol) prior to ethanol access. Neither concentration of ghrelin resulted in a significant increase in 8% ethanol consumption of VSG or control subjects. Next, the rats were given IP injections of the ghrelin receptor antagonist, JMV (2.5 mg/kg body weight). This dose induced a significant reduction in 8% ethanol consumption in the VSG group, but no effect on ethanol intake in the controls. While ghrelin injection was uninformative, increased sensitivity to subthreshold doses of the ghrelin receptor antagonist may indicate reduced ghrelin signaling following VSG. Overall, these findings suggest that bariatric patients with increased susceptibility to AUD may benefit from receiving VSG instead of RYGB surgery, and that changes in ghrelin signaling, at least in part, may play a role in the differential AUD risks between the two most commonly performed bariatric surgical procedures.
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