Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA.
Department of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, 17033, USA.
Brain Res Bull. 2018 Apr;138:26-36. doi: 10.1016/j.brainresbull.2017.08.004. Epub 2017 Aug 9.
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 (2.5nmol and 5nmol) 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 (2.5mg/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.
胃袖状切除术（VSG）和 Roux-en-Y 胃旁路术（RYGB）是治疗肥胖和代谢紊乱的最常见手术选择。虽然 RYGB 可能导致更大和更持久的体重减轻，但最近在大鼠的临床和临床前研究引起了人们的关注，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 AUD 的风险较低，尽管尚未进行临床前研究来证实这一点。因此，本研究旨在使用类似于先前用于 RYGB 动物研究的方案，确定 VSG 对肥胖大鼠和小鼠模型中乙醇摄入和偏好的影响。雄性 Sprague Dawley 大鼠和雄性 C57B6 小鼠在高脂肪饮食（60%卡路里来自脂肪）上肥胖，并接受 VSG 或无手术（对照）。所有动物都被给予了不同浓度的乙醇（2%、4%、6%和 8%），并在几天内进行了测试。与对照组相比，VSG 大鼠消耗的 2%、6%和 8%乙醇明显减少，对 6%和 8%乙醇与水的偏好明显降低。VSG 小鼠也表现出对 6%和 8%乙醇溶液的摄入和偏好减少。在两周的强制禁欲期后，重新引入 8%乙醇，VSG 大鼠和小鼠继续表现出对乙醇的消耗和偏好减少。关于潜在机制，我们假设 VSG 手术中胃饥饿素产生部分的切除可能是观察到的乙醇偏好减少的原因之一。为了测试胃饥饿素受体的功能变化，VSG 和对照大鼠在接触乙醇之前接受了 IP 注射酰基胃饥饿素（2.5nmol 和 5nmol）。两种浓度的胃饥饿素都没有导致 VSG 或对照组 subjects 对 8%乙醇消耗的显著增加。接下来，大鼠接受了 IP 注射胃饥饿素受体拮抗剂 JMV（2.5mg/kg 体重）。该剂量在 VSG 组中显著降低了 8%乙醇的消耗，但对对照组的乙醇摄入没有影响。虽然胃饥饿素注射没有提供信息，但对亚阈值剂量的胃饥饿素受体拮抗剂的敏感性增加可能表明 VSG 后胃饥饿素信号减少。总体而言，这些发现表明，对 AUD 易感性增加的肥胖患者可能受益于接受 VSG 而不是 RYGB 手术，并且胃饥饿素信号的变化至少部分可能在两种最常进行的减肥手术之间的不同 AUD 风险中发挥作用。
