Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.
J Neuroendocrinol. 2021 Jan;33(1):e12913. doi: 10.1111/jne.12913. Epub 2020 Nov 10.
Bariatric surgery is the most effective and durable means of treating obesity and its comorbidities. Women make up 80% of those receiving weight loss surgery and they experience improvements in fertility. Unfortunately, bariatric surgery in the context of pregnancy is associated with complications, including growth restriction and small-for-gestational age offspring (SGA). SGA offspring have a greater risk for obesity in adulthood, although the mechanism for this SGA-induced obesity is unknown. In a rat model of vertical sleeve gastrectomy (VSG), we previously identified reductions during pregnancy in ghrelin, a stomach-derived hormone that increases appetite and induces growth hormone secretion. Here, we hypothesise that VSG offspring will have altered ghrelin signalling compared to offspring of Sham dams as a result of reduced in utero ghrelin. At postnatal day (PND)21, male and female offspring of dams that have previously received VSG have an increase in mRNA expression for the ghrelin receptor in the hypothalamus compared to Sham offspring, and the expression of GOAT is lower in females compared to males. Liver expression of endogenous ghrelin antagonist, LEAP2, is elevated at PND60 in VSG offspring. Expression of other genes in the growth hormone system (growth hormone-releasing hormone and growth hormone) were not altered. Plasma levels of total ghrelin at PND21 are also not different between VSG and Sham pups. In adult pups, 1-hour chow intake of male but not female VSG offspring given is less than Sham offspring when given 50 µg kg of exogenous ghrelin by i.p. injection. These results indicate that maternal VSG surgery has an impact on ghrelin signalling in offspring and that, as adults, male VSG offspring may be functionally less responsive to ghrelin than controls.
减重手术是治疗肥胖及其合并症最有效和持久的方法。接受减肥手术的患者中有 80%是女性，她们的生育能力得到了改善。不幸的是，妊娠期间的减重手术与并发症有关，包括生长受限和小于胎龄儿（SGA）。SGA 后代成年后患肥胖的风险更高，尽管这种 SGA 诱导肥胖的机制尚不清楚。在垂直袖状胃切除术（VSG）的大鼠模型中，我们之前发现妊娠期间胃泌素减少，胃泌素是一种增加食欲并诱导生长激素分泌的激素。在这里，我们假设与 Sham 对照组相比，VSG 后代的胃泌素信号会发生改变，因为其宫内胃泌素减少。在产后第 21 天（PND21），与 Sham 对照组相比，之前接受过 VSG 的母鼠的雄性和雌性后代的下丘脑 ghrelin 受体的 mRNA 表达增加，并且与雄性相比，雌性的 GOAT 表达降低。在 VSG 后代中，肝内源性 ghrelin 拮抗剂 LEAP2 的表达在 PND60 时升高。生长激素系统（生长激素释放激素和生长激素）中的其他基因的表达没有改变。PND21 时 VSG 和 Sham 幼鼠的总胃泌素血浆水平也没有差异。在成年幼鼠中，当通过腹腔注射给予 50µg/kg 的外源性胃泌素时，雄性但不是雌性 VSG 后代的 1 小时进食量小于 Sham 对照组。这些结果表明，母体 VSG 手术对后代的胃泌素信号有影响，并且作为成年人，雄性 VSG 后代对胃泌素的反应可能不如对照组敏感。
