The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, USA.
The Pennsylvania State University College of Medicine, Department of Neural and Behavioral Sciences, USA.
Brain Res Bull. 2022 Oct 1;188:179-186. doi: 10.1016/j.brainresbull.2022.07.019. Epub 2022 Jul 25.
The weight-loss surgery Roux-en Y gastric bypass (RYGB) is a relatively effective, long-term treatment option for patients with morbid obesity. However, accumulating clinical evidence suggests that patients receiving RYGB may be at increased risk of developing alcohol use disorder. This observation has been repeatedly supported by preclinical studies showing rodents increase intake of ethanol (EtOH) after RYGB, and has been further confirmed by human studies. A promising alternative to RYGB is sleeve gastrectomy (SG), which has resulted in decreased EtOH consumption in some rodent studies. The exact mechanism underlying the differential alcohol outcomes after RYGB versus SG has yet to be elucidated. However, the gut hormone ghrelin has emerged as a potential candidate from previous preclinical studies specific to RYGB surgeries and due to its action to stimulate food and alcohol intake and cravings. To directly assess changes in plasma ghrelin levels following weigh loss surgeries in the context of alcohol intake, 24 female rats were separated into three surgical groups receiving RYGB, SG, or Sham surgery followed by caloric restriction to produce adiposity matched controls (Sham-AM). Blood was drawn for fasted and fed plasma ghrelin (acyl and des-acyl) assays at multiple time points: while on a normal diet (ND), after 5-week exposure to a high fat diet (HFD), following surgery, and after a series of two-bottle alcohol choice test with increasing concentrations (2%, 4%, 6%, 8%) of EtOH. Consistent with previous observations, RYGB rats drank more EtOH than SG rats across all concentrations. As expected, fasted ghrelin levels were blunted after HFD feeding, compared to normal diet baseline. After RYGB, fasted ghrelin levels returned to higher levels while remained blunted after SG and Sham-AM. Fed acyl ghrelin levels were significantly increased to above "normal" levels after RYGB, but remain low after SG and Sham-AM. Given that post-RYGB acyl ghrelin levels are raised to a fasted state regardless of actual prandial status, we conclude that RYGB may results in a hormonal state reminiscence of a fasted state with the inability of feeding to inhibit ghrelin production, an effect which could potentially contribute to increased EtOH intake following the surgery. In contrast, following SG, ghrelin levels in rats remain consistent with the fed state regardless of prandial status, potentially explaining lower alcohol intake and lower risk of developing AUD.
减重手术 Roux-en Y 胃旁路术（RYGB）是一种针对病态肥胖症患者相对有效的长期治疗选择。然而，越来越多的临床证据表明，接受 RYGB 的患者可能面临更高的酒精使用障碍风险。这一观察结果得到了多项临床前研究的反复支持，这些研究表明，接受 RYGB 后的啮齿动物会增加乙醇（EtOH）的摄入量，而人类研究也进一步证实了这一点。RYGB 的一种有前途的替代方法是袖状胃切除术（SG），一些啮齿动物研究表明，SG 可减少 EtOH 的摄入。RYGB 与 SG 后酒精结果差异的确切机制尚未阐明。然而，胃激素 ghrelin 已从之前特定于 RYGB 手术的临床前研究中脱颖而出，并且由于其刺激食物和酒精摄入和渴望的作用，成为一个潜在的候选者。为了直接评估减肥手术后血浆 ghrelin 水平在酒精摄入方面的变化，将 24 只雌性大鼠分为三组，分别接受 RYGB、SG 或假手术，然后进行热量限制，以产生肥胖匹配的对照组（Sham-AM）。在多个时间点抽取禁食和进食时的血浆 ghrelin（酰基和脱酰基）检测：在正常饮食（ND）期间、5 周高脂肪饮食（HFD）暴露后、手术后以及一系列增加浓度（2%、4%、6%、8%）的乙醇双瓶酒精选择测试后。与之前的观察结果一致，RYGB 大鼠在所有浓度下的 EtOH 摄入量均高于 SG 大鼠。正如预期的那样，与正常饮食基线相比，HFD 喂养后空腹 ghrelin 水平降低。RYGB 后，空腹 ghrelin 水平恢复到较高水平，但 SG 和 Sham-AM 后仍较低。进食时酰基 ghrelin 水平显着升高至高于“正常”水平，但 SG 和 Sham-AM 后仍较低。由于 RYGB 后酰基 ghrelin 水平升高至空腹状态，无论实际进食状态如何，我们得出结论，RYGB 可能导致激素状态类似于空腹状态，而进食无法抑制 ghrelin 的产生，这种效应可能会导致手术后 EtOH 摄入量增加。相比之下，接受 SG 后，大鼠的 ghrelin 水平无论进食状态如何都与进食状态一致，这可能解释了较低的酒精摄入量和较低的 AUD 风险。
